Wnts are secreted,lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways,which control various biological processes throughout embryo...Wnts are secreted,lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways,which control various biological processes throughout embryonic development and adult life.Aberrant Wnt signaling pathway underlies a wide range of human disease pathogeneses.展开更多
Mechanical stimuli play an essential role in maintaining bone remodeling and skeletal integrity.Meanwhile,bone can respond to the changes of mechanical condition to adjust its mass and architecture.Clinical studies di...Mechanical stimuli play an essential role in maintaining bone remodeling and skeletal integrity.Meanwhile,bone can respond to the changes of mechanical condition to adjust its mass and architecture.Clinical studies discover that bedridden patients showed osteoporotic T-scores and low bone mineral density,and long-term immobilized patients presented reduced markers of bone formation.However,as bone formation mediated by osteoblast differentiation is a complex process,the underlying molecular mechanism of mechanical stimuli regulating bone formation is still unclear.Recent evidences show that microRNAs(miRNAs)are involved in mechanical stimuli regulating bone formation or osteoblast differentiation.Nevertheless,no direct evidence identifies mechanoresponsive miRNA in both human and animal bones,and clarifies its mechanoresponsive role under different mechanical conditions(e.g.mechanical unloading,reloading,loading).In the current study,we screened for differentially expressed miRNAs in bone specimens of bedridden patients with fractures,then identified that the expression of miR-138-5p,but not the other miRNAs,altered withbedridden time and was negatively correlated with the expression of the bone formation marker genes Alp(alkaline phosphatase).Moreover,miR-138-5p was up-regulated with reduced bone formation during unloading and down-regulated with increased bone formation during reloading in hind4imb unloaded mice.In addition,miR-138-5p was verified to be responsive to different mechanical unloading condition and cyclic mechanical stretch condition in primary osteogenic cells,respectively.Further in vitro data suggested that mechanoresponsive miR-138-5p directly targeted microtubule actin crosslinking factor 1(MACF1)to inhibit osteoblast differentiation.In vivo,we constructed an osteoblastic miR-138-5p transgenic mice model(TG138)with the Runx2promoter,and found that overexpression miR-138-5p supressed bone formation.Moreover,osteoblast-targeted inhibition of miR-138-5p sensitized bone anabolic response to mechanical loading in TG138 mice.Predominantly,the osteoblast-targeted inhibition of miR-138-5p could counteract bone formation reduction induced by hind limb unloading.Taken together,the mechanoresponsive miR-138-5p inhibited bone anabolic response for developing a novel bone anabolic sensitization strategy.展开更多
With the development of manned spaceflight, more and more researches are involved in the area of gravitation physiology. When astronauts are exposed to microgravity, a series of special physiological or pathological c...With the development of manned spaceflight, more and more researches are involved in the area of gravitation physiology. When astronauts are exposed to microgravity, a series of special physiological or pathological changes will occur, which will start self-regulation mechanisms to reduce abnormalities and help the organism to better adapt to microgravity. However, these adaptive changes may also induce degradation or damage to physiological functions. This paper summarizes the physiological effects of microgravity on the human body from the aspects of skeletal and mineral metabolism, muscle structure and function, vestibular functions, cardiovascular function and pulmonary function, as well as expounds some commonly used ground-based space analogies. The paper will provide a reference for further study on the physiological effects of microgravity.展开更多
As a key coordinator of metabolism,AMP-activated protein kinase(AMPK)is vitally involved in skeletal muscle maintenance.AMPK exerts its cellular effects through its function as a serine/threonine protein kinase by reg...As a key coordinator of metabolism,AMP-activated protein kinase(AMPK)is vitally involved in skeletal muscle maintenance.AMPK exerts its cellular effects through its function as a serine/threonine protein kinase by regulating many downstream targets and plays important roles in the development and growth of skeletal muscle.AMPK is activated by phosphorylation and exerts its function as a kinase in many processes,including synthesis and degradation of proteins,mitochondrial biogenesis,glucose uptake,and fatty acid and cholesterol metabolism.Skeletal muscle atrophy is a result of various diseases or disorders and is characterized by a decrease in muscle mass.The pathogenesis and therapeutic strategies of skeletal muscle atrophy are still under investigation.In this review,we discuss the role of AMPK in skeletal muscle metabolism and atrophy.We also discuss targeting AMPK for skeletal muscle treatment,including exercise,AMPK activators including 5-amino-4-imidazolecarboxamide ribonucleoside and metformin,and low-level lasers.These studies show the important roles of AMPK in regulating muscle metabolism and function;thus,the treatment of skeletal muscle atrophy needs to take into account the roles of AMPK.展开更多
The decreased osteoblast differentiation associated with reduced bone formation is one main cause of microgravityinduced bone loss.Our previous studies have demonstrated that microtubule actin crosslinking factor 1(MA...The decreased osteoblast differentiation associated with reduced bone formation is one main cause of microgravityinduced bone loss.Our previous studies have demonstrated that microtubule actin crosslinking factor 1(MACF1)is downregulated in association with the decreased osteoblast differentiation and bone formation under simulated microgravity conditions.These findings suggest that MACF1 is sensitive to mechanical condition and may be critical for osteoblast differentiation and bone formation.To verify this hypothesis,current study investigates the role and mechanism of MACF1 in regulatingosteoblast differentiation by adopting MACF1 knockdown(MACF1-KD)osteoblasts.The results showed that MACF1 knockdown suppressed mineralized nodules formation,alkaline phosphatase(ALP)activity,osteogenic gene expression andβ-catenin signaling transduction.Moreover,we used RNA sequencing(RNA-seq)and chromatin immunoprecipitation sequencing(ChIP-seq)to investigate further mechanism.Interestingly,we found that MACF1 sequesterd repressors of osteoblast differentiation in cytoplasm.In conclusion,MACF1 is sensitive to mechanical condition and plays key role in activatingβ-catenin signaling transduction and sequestering repressors of osteoblast differentiation,which further promotes osteoblast differentiation.展开更多
Tooth mineralization is a ubiquitous and tightly regulated process involving complicated interactions between dental epithelium and mesenchyme.Key molecules in tooth mineralization remain poorly identified.Microtubule...Tooth mineralization is a ubiquitous and tightly regulated process involving complicated interactions between dental epithelium and mesenchyme.Key molecules in tooth mineralization remain poorly identified.Microtubule actin cross-linking factor 1(MACF1)is a spectraplakin protein that plays pivotal roles in the brain,muscle,lung,and bone developmental process.^(1-3) To study the specific functions of MACF1 in bone formation,we established Macf1 conditional knockout mice using the Cre-LoxP system driven by Osxterix promoter(Osx-Cre;Macf1^(f/f)).^(2) Not surprisingly,Osx-Cre;Macf1^(f/f) mice displayed the phenotypes of delayed ossification and decreased bone mass.Moreover,the OsxCre;Macf1^(f/f) mice unexpectedly showed a white and opaque appearance of incisors,contrary to the normal yellowbrown and transparent incisors.Since Osxterix is expressed in dental mesenchyme during tooth development,the abnormal tooth appearance might imply a new function of MACF1 in odontoblasts,or even ameloblasts.Therefore,the present study aimed to investigate the role of MACF1 during tooth development.展开更多
Objective:Osteoporosis has become the biggest cause of non-fatal health issue.Currently,the limitations of traditional anti-osteoporosis drugs such as long-term ill-effects and drug resistance,have raised concerns tow...Objective:Osteoporosis has become the biggest cause of non-fatal health issue.Currently,the limitations of traditional anti-osteoporosis drugs such as long-term ill-effects and drug resistance,have raised concerns toward complementary and alternative therapies,particularly herbal medicines and their natural active compounds.Thus,this study aimed to provide an integrative analysis of active chemicals,drug targets and interacting pathways of the herbs for osteoporosis treatment.Methods:Here,we introduced a systematic pharmacology model,combining the absorption,distribution,metabolism,and excretion(ADME)screening model,drug targeting and network pharmacology,to probe into the therapeutic mechanisms of herbs in osteoporosis.Results:We obtained 86 natural compounds with favorable pharmacokinetic profiles and their 58 targets from seven osteoporosis-related herbs.Network analysis revealed that they probably synergistically work through multiple mechanisms,such as suppressing inflammatory response,maintaining bone metabolism or improving organism immunity,to benefit patients with osteoporosis.Furthermore,experimental results showed that all the five compounds(calycosin,asperosaponin VI,hederagenin,betulinic acid and luteolin)enhanced osteoblast proliferation and differentiation in vitro,which corroborated the validity of this system pharmacology approach.Notably,gentisin and aureusidin among the identified compounds were first predicted to be associated with osteoporosis.Conclusion:Herbs and their natural compounds,being characterized as the classical combination therapies,might be engaged in multiple mechanisms to coordinately improve the osteoporosis symptoms.This work may contribute to offer novel strategies and clues for the therapy and drug discovery of osteoporosis and other complex diseases.展开更多
Lung metastasis is the primary cause of death in osteosarcoma(OS)patients.1 A better understanding of the molecular mechanisms underlying OS tumorigenesis and metastasis is urgently needed to identify therapeutic targ...Lung metastasis is the primary cause of death in osteosarcoma(OS)patients.1 A better understanding of the molecular mechanisms underlying OS tumorigenesis and metastasis is urgently needed to identify therapeutic targets.Microtubule actin crosslinking factor 1(MACF1),which belongs to the spectraplakin family of cytoskeletal crosslinking proteins,2 is critical for cell migration and polarization due to its regulation of the cytoskeleton.Recently,MACF1 was indicated to be involved in the metastatic invasion of some human cancers,3 but the function of MACF1 in OS is still unclear.展开更多
Osteoporosis is a prevalent multifactorial bone disease with a strong genetic contribution.The heritability of traits that contribute to osteoporosis(bone mass,bone mineral density(BMD),bone size,bone loss and fractur...Osteoporosis is a prevalent multifactorial bone disease with a strong genetic contribution.The heritability of traits that contribute to osteoporosis(bone mass,bone mineral density(BMD),bone size,bone loss and fractures)ranges from 50 to 85%,suggesting that a comprehensive understanding of the genetic basis may help identify new therapeutic targets.1 However,the genetic characteristics remain obscure,and the existing drug targets are associated with various challenges.Numerous studies have demonstrated that high-throughput sequencing data analysis is fruitful for identifying novel targets of human diseases.2 We therefore integrated GWAS and transcriptome analyses through Multi-marker Analysis of GenoMic Annotation(MAGMA)and weighted gene co-expression network analysis3(WGCNA)to identify new network modules and potential therapeutic genes for osteoporosis.As an illustration,the flow chart presenting the process of the present study was shown in Figure S1.展开更多
Purpose:Blast lung injury(BLI)is the most common damage resulted from explosion-derived shock wave in military,terrorism and industrial accidents.However,the molecular mechanisms underlying BLI induced by shock wave a...Purpose:Blast lung injury(BLI)is the most common damage resulted from explosion-derived shock wave in military,terrorism and industrial accidents.However,the molecular mechanisms underlying BLI induced by shock wave are still unclear.Methods:In this study,a goat BLI model was established by a fuel air explosive power.The key genes involved in were identified.The goats of the experimental group were fixed on the edge of the explosion cloud,while the goats of the control group were 3 km far away from the explosive environment.After successful modeling for 24 h,all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing.Gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)analysis were performed to identify the main enriched biological functions of differentially expressed genes(DEGs).Quantitative real-time polymerase chain reaction(qRT-PCR)was used to verify the consistency of gene expression.Results:Of the sampled goat lungs,895 genes were identified to be significantly differentially expressed,and they were involved in 52 significantly enriched GO categories.KEGG analysis revealed that DEGs were highly enriched in 26 pathways,such as cytokine-cytokine receptor interaction,antifolate resistance,arachidonic acid metabolism,amoebiasis and bile secretion,JAK-STAT,and IL-17 signaling pathway.Furthermore,15 key DEGs involved in the biological processes of BLI were confirmed by qRTPCR,and the results were consistent with RNA sequencing.Conclusion:Gene expression profiling provide a better understanding of the molecular mechanisms of BLI,which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.展开更多
基金supported by the National Natural Science Foundation of China (81772017 to[L.F.H.],and 82072106 and 32371371 to[A.R.Q.])The Project Supported by Natural Science Basic Research Plan in Shaanxi Province of China (2023-JC-YB-163 to[L.F.H.])the National Institutes of Health[AR-070135 and AG-056438 to W.C.,and AR075735,DE023813,AR074954,and DE028264 to Y.P.L.]。
文摘Wnts are secreted,lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways,which control various biological processes throughout embryonic development and adult life.Aberrant Wnt signaling pathway underlies a wide range of human disease pathogeneses.
基金supported by the National Natural Science Foundation of China ( 31570940,81772017)
文摘Mechanical stimuli play an essential role in maintaining bone remodeling and skeletal integrity.Meanwhile,bone can respond to the changes of mechanical condition to adjust its mass and architecture.Clinical studies discover that bedridden patients showed osteoporotic T-scores and low bone mineral density,and long-term immobilized patients presented reduced markers of bone formation.However,as bone formation mediated by osteoblast differentiation is a complex process,the underlying molecular mechanism of mechanical stimuli regulating bone formation is still unclear.Recent evidences show that microRNAs(miRNAs)are involved in mechanical stimuli regulating bone formation or osteoblast differentiation.Nevertheless,no direct evidence identifies mechanoresponsive miRNA in both human and animal bones,and clarifies its mechanoresponsive role under different mechanical conditions(e.g.mechanical unloading,reloading,loading).In the current study,we screened for differentially expressed miRNAs in bone specimens of bedridden patients with fractures,then identified that the expression of miR-138-5p,but not the other miRNAs,altered withbedridden time and was negatively correlated with the expression of the bone formation marker genes Alp(alkaline phosphatase).Moreover,miR-138-5p was up-regulated with reduced bone formation during unloading and down-regulated with increased bone formation during reloading in hind4imb unloaded mice.In addition,miR-138-5p was verified to be responsive to different mechanical unloading condition and cyclic mechanical stretch condition in primary osteogenic cells,respectively.Further in vitro data suggested that mechanoresponsive miR-138-5p directly targeted microtubule actin crosslinking factor 1(MACF1)to inhibit osteoblast differentiation.In vivo,we constructed an osteoblastic miR-138-5p transgenic mice model(TG138)with the Runx2promoter,and found that overexpression miR-138-5p supressed bone formation.Moreover,osteoblast-targeted inhibition of miR-138-5p sensitized bone anabolic response to mechanical loading in TG138 mice.Predominantly,the osteoblast-targeted inhibition of miR-138-5p could counteract bone formation reduction induced by hind limb unloading.Taken together,the mechanoresponsive miR-138-5p inhibited bone anabolic response for developing a novel bone anabolic sensitization strategy.
文摘With the development of manned spaceflight, more and more researches are involved in the area of gravitation physiology. When astronauts are exposed to microgravity, a series of special physiological or pathological changes will occur, which will start self-regulation mechanisms to reduce abnormalities and help the organism to better adapt to microgravity. However, these adaptive changes may also induce degradation or damage to physiological functions. This paper summarizes the physiological effects of microgravity on the human body from the aspects of skeletal and mineral metabolism, muscle structure and function, vestibular functions, cardiovascular function and pulmonary function, as well as expounds some commonly used ground-based space analogies. The paper will provide a reference for further study on the physiological effects of microgravity.
基金supported by the Natural Science Foundation of China(Grant No.32071517,82072106)the Natural Science Basic Research Plan in Shaanxi Province of China(Grant No.2020JM-100).
文摘As a key coordinator of metabolism,AMP-activated protein kinase(AMPK)is vitally involved in skeletal muscle maintenance.AMPK exerts its cellular effects through its function as a serine/threonine protein kinase by regulating many downstream targets and plays important roles in the development and growth of skeletal muscle.AMPK is activated by phosphorylation and exerts its function as a kinase in many processes,including synthesis and degradation of proteins,mitochondrial biogenesis,glucose uptake,and fatty acid and cholesterol metabolism.Skeletal muscle atrophy is a result of various diseases or disorders and is characterized by a decrease in muscle mass.The pathogenesis and therapeutic strategies of skeletal muscle atrophy are still under investigation.In this review,we discuss the role of AMPK in skeletal muscle metabolism and atrophy.We also discuss targeting AMPK for skeletal muscle treatment,including exercise,AMPK activators including 5-amino-4-imidazolecarboxamide ribonucleoside and metformin,and low-level lasers.These studies show the important roles of AMPK in regulating muscle metabolism and function;thus,the treatment of skeletal muscle atrophy needs to take into account the roles of AMPK.
基金supported by the National Natural Science Foundation of China ( 81772017,31570940)Young Talent Fund of University Association for Science and Technology in Shaanxi,China ( 20170401)Supported by Natural Science Basic Research Plan in Shaanxi Province of China ( 2018JM3040)
文摘The decreased osteoblast differentiation associated with reduced bone formation is one main cause of microgravityinduced bone loss.Our previous studies have demonstrated that microtubule actin crosslinking factor 1(MACF1)is downregulated in association with the decreased osteoblast differentiation and bone formation under simulated microgravity conditions.These findings suggest that MACF1 is sensitive to mechanical condition and may be critical for osteoblast differentiation and bone formation.To verify this hypothesis,current study investigates the role and mechanism of MACF1 in regulatingosteoblast differentiation by adopting MACF1 knockdown(MACF1-KD)osteoblasts.The results showed that MACF1 knockdown suppressed mineralized nodules formation,alkaline phosphatase(ALP)activity,osteogenic gene expression andβ-catenin signaling transduction.Moreover,we used RNA sequencing(RNA-seq)and chromatin immunoprecipitation sequencing(ChIP-seq)to investigate further mechanism.Interestingly,we found that MACF1 sequesterd repressors of osteoblast differentiation in cytoplasm.In conclusion,MACF1 is sensitive to mechanical condition and plays key role in activatingβ-catenin signaling transduction and sequestering repressors of osteoblast differentiation,which further promotes osteoblast differentiation.
基金the National Natural Science Foundation of China(No.30970706,81700784,81974145)the Fundamental Research Funds for the Central Universities(China)(No.D5000210746)+2 种基金the Key Research and Development Project of Shaanxi Province(China)(No.2021SF-293,2021SF-242)the Talent Introduction Project of Sichuan University of Science and Engineering(No.2022RC01)the Guangdong Basic and Applied Basic Research Foundation(China)(No.2023A1515030047).
文摘Tooth mineralization is a ubiquitous and tightly regulated process involving complicated interactions between dental epithelium and mesenchyme.Key molecules in tooth mineralization remain poorly identified.Microtubule actin cross-linking factor 1(MACF1)is a spectraplakin protein that plays pivotal roles in the brain,muscle,lung,and bone developmental process.^(1-3) To study the specific functions of MACF1 in bone formation,we established Macf1 conditional knockout mice using the Cre-LoxP system driven by Osxterix promoter(Osx-Cre;Macf1^(f/f)).^(2) Not surprisingly,Osx-Cre;Macf1^(f/f) mice displayed the phenotypes of delayed ossification and decreased bone mass.Moreover,the OsxCre;Macf1^(f/f) mice unexpectedly showed a white and opaque appearance of incisors,contrary to the normal yellowbrown and transparent incisors.Since Osxterix is expressed in dental mesenchyme during tooth development,the abnormal tooth appearance might imply a new function of MACF1 in odontoblasts,or even ameloblasts.Therefore,the present study aimed to investigate the role of MACF1 during tooth development.
基金supported by the National Natural Science Foundation of China under No.81901917 and No.31570940the key grant BKJ17J004 and the Key Research and Development Project of Shaanxi Province under No.2018SF-363+1 种基金China’s Post-doctoral Science Fund under No.2017M623249the Fundamental Research Funds for the Central Universities under No.3102017OQD050。
文摘Objective:Osteoporosis has become the biggest cause of non-fatal health issue.Currently,the limitations of traditional anti-osteoporosis drugs such as long-term ill-effects and drug resistance,have raised concerns toward complementary and alternative therapies,particularly herbal medicines and their natural active compounds.Thus,this study aimed to provide an integrative analysis of active chemicals,drug targets and interacting pathways of the herbs for osteoporosis treatment.Methods:Here,we introduced a systematic pharmacology model,combining the absorption,distribution,metabolism,and excretion(ADME)screening model,drug targeting and network pharmacology,to probe into the therapeutic mechanisms of herbs in osteoporosis.Results:We obtained 86 natural compounds with favorable pharmacokinetic profiles and their 58 targets from seven osteoporosis-related herbs.Network analysis revealed that they probably synergistically work through multiple mechanisms,such as suppressing inflammatory response,maintaining bone metabolism or improving organism immunity,to benefit patients with osteoporosis.Furthermore,experimental results showed that all the five compounds(calycosin,asperosaponin VI,hederagenin,betulinic acid and luteolin)enhanced osteoblast proliferation and differentiation in vitro,which corroborated the validity of this system pharmacology approach.Notably,gentisin and aureusidin among the identified compounds were first predicted to be associated with osteoporosis.Conclusion:Herbs and their natural compounds,being characterized as the classical combination therapies,might be engaged in multiple mechanisms to coordinately improve the osteoporosis symptoms.This work may contribute to offer novel strategies and clues for the therapy and drug discovery of osteoporosis and other complex diseases.
基金supported by the National Natural Science Foundation of China(No.81801871)the Shaanxi Provincial Key R&D Program(No.2021SF-293,2018KWZ-10,2018SF-363)+1 种基金the Special Fund for Technological Innovation of Shaanxi Province(No.2019QYPY-207)the Fundamental Research Funds for the Central Universities(No.3102018zy053,D5000210746).
文摘Lung metastasis is the primary cause of death in osteosarcoma(OS)patients.1 A better understanding of the molecular mechanisms underlying OS tumorigenesis and metastasis is urgently needed to identify therapeutic targets.Microtubule actin crosslinking factor 1(MACF1),which belongs to the spectraplakin family of cytoskeletal crosslinking proteins,2 is critical for cell migration and polarization due to its regulation of the cytoskeleton.Recently,MACF1 was indicated to be involved in the metastatic invasion of some human cancers,3 but the function of MACF1 in OS is still unclear.
基金supported by the Natural Science Foundation of China(No.82072106,81700784 and 32101055)China Postdoctoral Science Foundation(No.2020M683573 and 2017M613196+2 种基金the Natural Science Foundation of Shaanxi Province(No.2021JQ-128)the Key R&D Projects in Shaanxi Province(No.2021SF-242)the Fundamental Research Funds for the Central Universities(No.D5000210746).
文摘Osteoporosis is a prevalent multifactorial bone disease with a strong genetic contribution.The heritability of traits that contribute to osteoporosis(bone mass,bone mineral density(BMD),bone size,bone loss and fractures)ranges from 50 to 85%,suggesting that a comprehensive understanding of the genetic basis may help identify new therapeutic targets.1 However,the genetic characteristics remain obscure,and the existing drug targets are associated with various challenges.Numerous studies have demonstrated that high-throughput sequencing data analysis is fruitful for identifying novel targets of human diseases.2 We therefore integrated GWAS and transcriptome analyses through Multi-marker Analysis of GenoMic Annotation(MAGMA)and weighted gene co-expression network analysis3(WGCNA)to identify new network modules and potential therapeutic genes for osteoporosis.As an illustration,the flow chart presenting the process of the present study was shown in Figure S1.
基金This work was supported by Science and Technology Development Fund for Institute for Hygiene of Ordnance(KY202007).
文摘Purpose:Blast lung injury(BLI)is the most common damage resulted from explosion-derived shock wave in military,terrorism and industrial accidents.However,the molecular mechanisms underlying BLI induced by shock wave are still unclear.Methods:In this study,a goat BLI model was established by a fuel air explosive power.The key genes involved in were identified.The goats of the experimental group were fixed on the edge of the explosion cloud,while the goats of the control group were 3 km far away from the explosive environment.After successful modeling for 24 h,all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing.Gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)analysis were performed to identify the main enriched biological functions of differentially expressed genes(DEGs).Quantitative real-time polymerase chain reaction(qRT-PCR)was used to verify the consistency of gene expression.Results:Of the sampled goat lungs,895 genes were identified to be significantly differentially expressed,and they were involved in 52 significantly enriched GO categories.KEGG analysis revealed that DEGs were highly enriched in 26 pathways,such as cytokine-cytokine receptor interaction,antifolate resistance,arachidonic acid metabolism,amoebiasis and bile secretion,JAK-STAT,and IL-17 signaling pathway.Furthermore,15 key DEGs involved in the biological processes of BLI were confirmed by qRTPCR,and the results were consistent with RNA sequencing.Conclusion:Gene expression profiling provide a better understanding of the molecular mechanisms of BLI,which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.
