Objective Psoriasis is often combined with metabolic abnormalities,such as obesity and diabetes.The upregulation of chemerin,which is an essential protein produced primarily from white fat,is strongly correlated to th...Objective Psoriasis is often combined with metabolic abnormalities,such as obesity and diabetes.The upregulation of chemerin,which is an essential protein produced primarily from white fat,is strongly correlated to the development of psoriasis.However,there is no clarification on its exact function and mechanism in disease pathogenesis.The present study aims to determine its function and mechanism in disease pathogenesis.Methods The present study used a psoriasislike inflammatory cell model and imiquimod(IMQ)-induced mouse model to confirm whether chemerin is upregulated in psoriasis patients.Results Chemerin enhanced the keratinocyte proliferation,inflammatory cytokine secretion,and activation of the MAPK signaling pathway.Crucially,the intraperitoneal injection of neutralizing anti-chemerin antibody(ChAb)diminished the epidermal proliferation and inflammation in the IMQ-induced mouse model.Conclusion The present results indicate that chemerin promotes keratinocyte proliferation,and enhances the production of inflammatory cytokines,thereby aggravating the psoriasis.Thus,chemerin can be a prospective target for the treatment of psoriasis.展开更多
Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that ...Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.展开更多
基金supported by a grant from the National Natural Science Foundation of China(No.81974308).
文摘Objective Psoriasis is often combined with metabolic abnormalities,such as obesity and diabetes.The upregulation of chemerin,which is an essential protein produced primarily from white fat,is strongly correlated to the development of psoriasis.However,there is no clarification on its exact function and mechanism in disease pathogenesis.The present study aims to determine its function and mechanism in disease pathogenesis.Methods The present study used a psoriasislike inflammatory cell model and imiquimod(IMQ)-induced mouse model to confirm whether chemerin is upregulated in psoriasis patients.Results Chemerin enhanced the keratinocyte proliferation,inflammatory cytokine secretion,and activation of the MAPK signaling pathway.Crucially,the intraperitoneal injection of neutralizing anti-chemerin antibody(ChAb)diminished the epidermal proliferation and inflammation in the IMQ-induced mouse model.Conclusion The present results indicate that chemerin promotes keratinocyte proliferation,and enhances the production of inflammatory cytokines,thereby aggravating the psoriasis.Thus,chemerin can be a prospective target for the treatment of psoriasis.
基金National Key R&D Program of China,Nos.2019YFA0110300 (to LZ),2021YFA1201400 (to LZ)Natural Science Foundation of Shanghai,No.21ZR1468600 (to LZ)Open Fund of the Key Laboratory of Cellular Physiology (Shanxi Medical University),Ministry of Education,No.KLMEC/SXMU-201910 (to XJ)。
文摘Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.
