The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate(ATP)by supporting cells in the Kölliker’s organ.However,the mechani...The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate(ATP)by supporting cells in the Kölliker’s organ.However,the mechanisms responsible for initiating spontaneous ATP release have not been determined.Our previous study revealed that telomerase reverse transcriptase(TERT)is expressed in the basilar membrane during the first postnatal week.Its role in cochlear development remains unclear.In this study,we investigated the expression and role of TERT in postnatal cochlea supporting cells.Our results revealed that in postnatal cochlear Kölliker’s organ supporting cells,TERT shifts from the nucleus into the cytoplasm over time.We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo.Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis,suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions.We observed increased ATP synthesis,release and activation of purine signaling systems in supporting cells during the first 10 postnatal days.The phenomenon that TERT translocation coincided with changes in ATP synthesis,release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system.Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.展开更多
Permanent damage to hair cells(HCs)is the leading cause of sensory deafness.Supporting cells(SCs)are essential in the restoration of hearing in mammals because they can proliferate and differentiate to HCs.MDS1 and EV...Permanent damage to hair cells(HCs)is the leading cause of sensory deafness.Supporting cells(SCs)are essential in the restoration of hearing in mammals because they can proliferate and differentiate to HCs.MDS1 and EVI1 complex locus(MECOM)is vital in early development and cell differentiation and regulates the TGF-βsignaling pathway to adapt to pathophysiological events,such as hematopoietic proliferation,differentiation and cells death.In addition,MECOM plays an essential role in neurogenesis and craniofacial development.However,the role of MECOM in the development of cochlea and its way to regulate related signaling are not fully understood.To address this problem,this study examined the expression of MECOM during the development of cochlea and observed a significant increase of MECOM at the key point of auditory epithelial morphogenesis,indicating that MECOM may have a vital function in the formation of cochlea and regeneration of HCs.Meanwhile,we tried to explore the possible effect and potential mechanism of MECOM in SC proliferation and HC regeneration.Findings from this study indicate that overexpression of MECOM markedly increases the proliferation of SCs in the inner ear,and the expression of Smad3 and Cdkn2b related to TGF signaling is significantly down-regulated,corresponding to the overexpression of MECOM.Collectively,these data may provide an explanation of the vital function of MECOM in SC proliferation and trans-differentiation into HCs,as well as its regulation.The interaction between MECOM,Wnt,Notch and the TGF-βsignaling may provide a feasible approach to induce the regeneration of HCs.展开更多
For many years, studies about the cochlea have been mainly focused on sensory cells, i.e. the inner hair cell(IHC) and outer hair cell (OHC), and the neuron system. Supporting cells, such as Hensen's cells and Dei...For many years, studies about the cochlea have been mainly focused on sensory cells, i.e. the inner hair cell(IHC) and outer hair cell (OHC), and the neuron system. Supporting cells, such as Hensen's cells and Deiters' cells are less studied. Their physiological functions and other characteristics are not well documented. Nowadays,supporting cells are a new world attracting to scientists' interests. The scope of this review is to detail the biological properties of the supporting cells, mainly Hensen's cells and Deiters' cells in the cochlea. Studies on this subject will be helpful in understanding physiology of the cochlea, and hopefully provide new approaches in treating diseases of inner ear.展开更多
Peripheral nerve injury is a common disease that endangers human health.There is a variety of methods to repair peripheral nerve injury,the current"gold standard"approach is autograft,however it still faces ...Peripheral nerve injury is a common disease that endangers human health.There is a variety of methods to repair peripheral nerve injury,the current"gold standard"approach is autograft,however it still faces many disadvantages.A new choice is the use of artificial nerve conduits,which are tubular structures and are designed to bridge nerve gaps.In order to bridge longer nerve gaps and gain ideal nerve regeneration effects,multiple technologies have been developed to the design of nerve conduits,such as selecting sutible materials,supplementing growth factors,transplanting supporting cells and so on.This review mainly introduce current progess in growth factors supplementation and supporting cells transplantation technology of nerve conduits.展开更多
Subject Code:H13With the support by the National Natural Science Foundation of China,the research team led by Prof.Li Huawei(李华伟)at the Otorhinolaryngology Department,Affiliated Eye and ENT hospital,State Key Labor...Subject Code:H13With the support by the National Natural Science Foundation of China,the research team led by Prof.Li Huawei(李华伟)at the Otorhinolaryngology Department,Affiliated Eye and ENT hospital,State Key Laboratory of Medical Neurobiology of Fudan University,achieved the mitotic hair cell generation through agenetic reprogramming procedure,which was published in the Journal of Neuroscience(2016,36(33):8734—8745).展开更多
Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regenera...Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased. Adenovirus encoding Atoh1 infected the sensory region and induced hair cell formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1 increased the Atoh1 expression level and decreased hes1 and hes5 levels, further promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1 activity to promote hair cell regeneration in rat cochlear sensory epithelium in vitro.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81870732(to DZ),82171161(to DZ),81900933(to YS),and 82000978(to ZL).
文摘The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate(ATP)by supporting cells in the Kölliker’s organ.However,the mechanisms responsible for initiating spontaneous ATP release have not been determined.Our previous study revealed that telomerase reverse transcriptase(TERT)is expressed in the basilar membrane during the first postnatal week.Its role in cochlear development remains unclear.In this study,we investigated the expression and role of TERT in postnatal cochlea supporting cells.Our results revealed that in postnatal cochlear Kölliker’s organ supporting cells,TERT shifts from the nucleus into the cytoplasm over time.We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo.Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis,suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions.We observed increased ATP synthesis,release and activation of purine signaling systems in supporting cells during the first 10 postnatal days.The phenomenon that TERT translocation coincided with changes in ATP synthesis,release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system.Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.
基金was supported by the Chinese National Natural Science Foundation of China(grant number 81371089)the Research Project of Wannan Medical College(grant number WK202122).
文摘Permanent damage to hair cells(HCs)is the leading cause of sensory deafness.Supporting cells(SCs)are essential in the restoration of hearing in mammals because they can proliferate and differentiate to HCs.MDS1 and EVI1 complex locus(MECOM)is vital in early development and cell differentiation and regulates the TGF-βsignaling pathway to adapt to pathophysiological events,such as hematopoietic proliferation,differentiation and cells death.In addition,MECOM plays an essential role in neurogenesis and craniofacial development.However,the role of MECOM in the development of cochlea and its way to regulate related signaling are not fully understood.To address this problem,this study examined the expression of MECOM during the development of cochlea and observed a significant increase of MECOM at the key point of auditory epithelial morphogenesis,indicating that MECOM may have a vital function in the formation of cochlea and regeneration of HCs.Meanwhile,we tried to explore the possible effect and potential mechanism of MECOM in SC proliferation and HC regeneration.Findings from this study indicate that overexpression of MECOM markedly increases the proliferation of SCs in the inner ear,and the expression of Smad3 and Cdkn2b related to TGF signaling is significantly down-regulated,corresponding to the overexpression of MECOM.Collectively,these data may provide an explanation of the vital function of MECOM in SC proliferation and trans-differentiation into HCs,as well as its regulation.The interaction between MECOM,Wnt,Notch and the TGF-βsignaling may provide a feasible approach to induce the regeneration of HCs.
文摘For many years, studies about the cochlea have been mainly focused on sensory cells, i.e. the inner hair cell(IHC) and outer hair cell (OHC), and the neuron system. Supporting cells, such as Hensen's cells and Deiters' cells are less studied. Their physiological functions and other characteristics are not well documented. Nowadays,supporting cells are a new world attracting to scientists' interests. The scope of this review is to detail the biological properties of the supporting cells, mainly Hensen's cells and Deiters' cells in the cochlea. Studies on this subject will be helpful in understanding physiology of the cochlea, and hopefully provide new approaches in treating diseases of inner ear.
基金Chinaprovince(2020376249,2019326481)the Natural Science Foundation of Ningbo(2013A6102647,2015A610207)。
文摘Peripheral nerve injury is a common disease that endangers human health.There is a variety of methods to repair peripheral nerve injury,the current"gold standard"approach is autograft,however it still faces many disadvantages.A new choice is the use of artificial nerve conduits,which are tubular structures and are designed to bridge nerve gaps.In order to bridge longer nerve gaps and gain ideal nerve regeneration effects,multiple technologies have been developed to the design of nerve conduits,such as selecting sutible materials,supplementing growth factors,transplanting supporting cells and so on.This review mainly introduce current progess in growth factors supplementation and supporting cells transplantation technology of nerve conduits.
文摘Subject Code:H13With the support by the National Natural Science Foundation of China,the research team led by Prof.Li Huawei(李华伟)at the Otorhinolaryngology Department,Affiliated Eye and ENT hospital,State Key Laboratory of Medical Neurobiology of Fudan University,achieved the mitotic hair cell generation through agenetic reprogramming procedure,which was published in the Journal of Neuroscience(2016,36(33):8734—8745).
基金supported by the National Natural Science Foundation of China,No.81420108010,81271084,81200740,81371093
文摘Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased. Adenovirus encoding Atoh1 infected the sensory region and induced hair cell formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1 increased the Atoh1 expression level and decreased hes1 and hes5 levels, further promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1 activity to promote hair cell regeneration in rat cochlear sensory epithelium in vitro.
