P311是一个由肺泡形成相关阶段相对于肺泡成熟期差减杂交文库中获得的上游调节基因,为探讨其在肺泡发生过程中的可能作用,本文以真实时间PCR(real time PCR)和免疫组织化学方法确定了P311在肺器官发育过程中的表达特点,结果显示P311的...P311是一个由肺泡形成相关阶段相对于肺泡成熟期差减杂交文库中获得的上游调节基因,为探讨其在肺泡发生过程中的可能作用,本文以真实时间PCR(real time PCR)和免疫组织化学方法确定了P311在肺器官发育过程中的表达特点,结果显示P311的表达无论在时间上还是在组织细胞分布上都与肺泡的发生密切相关.同时胎肺细胞植模型中,反义寡核苷酸阻断P311表达的研究亦显示P311在肺泡分隔膜形成过程中的重要性.展开更多
Background:P311,a highly conserved 8 kDa intracellular protein,has recently been reported to play an important role in aggravating hypertrophic scaring by promoting the differentiation and secretion of fibroblasts.Nev...Background:P311,a highly conserved 8 kDa intracellular protein,has recently been reported to play an important role in aggravating hypertrophic scaring by promoting the differentiation and secretion of fibroblasts.Nevertheless,how P311 regulates the differentiation and function of fibroblasts to affect granulation tissue formation remains unclear.In this work,we studied the underlying mechanisms via which P311 affects fibroblasts and promotes acute skin wound repair.Methods:To explore the role of P311,both in vitro and in vivo wound-healing models were used.Full-thickness skin excisional wounds were made in wild-type and P311−/−C57 adult mice.Wound healing rate,re-epithelialization,granulation tissue formation and collagen deposition were measured at days 3,6 and 9 after skin injury.The biological phenotypes of fibroblasts,the expression of target proteins and relevant signaling pathways were examined both in vitro and in vivo.Results:P311 could promote the proliferation and differentiation of fibroblasts,enhance the ability of myofibroblasts to secrete extracellular matrix and promote cell contraction,and then facilitate the formation of granulation tissue and eventually accelerate skin wound closure.Importantly,we discovered that P311 acts via up-regulating the expression of type II transforming growth factor-βreceptor(TGF-βRII)in fibroblasts and promoting the activation of the TGF-βRII-Smad signaling pathway.Mechanistically,the mammalian target of rapamycin signaling pathway is closely implicated in the regulation of the TGF-βRII-Smad pathway in fibroblasts mediated by P311.Conclusions:P311 plays a critical role in activation of the TGF-βRII-Smad pathway to promote fibroblast proliferation and differentiation as well as granulation tissue formation in the process of skin wound repair.展开更多
文摘P311是一个由肺泡形成相关阶段相对于肺泡成熟期差减杂交文库中获得的上游调节基因,为探讨其在肺泡发生过程中的可能作用,本文以真实时间PCR(real time PCR)和免疫组织化学方法确定了P311在肺器官发育过程中的表达特点,结果显示P311的表达无论在时间上还是在组织细胞分布上都与肺泡的发生密切相关.同时胎肺细胞植模型中,反义寡核苷酸阻断P311表达的研究亦显示P311在肺泡分隔膜形成过程中的重要性.
基金National Natural Sciences Foundation of China(No.31872742 to W.F.H.and No.81630055 to G.X.L.)Military Medical Science and Technology Youth Training Program of Army Military Medical University(Third Military Medical University)(No.20QNPY024 to W.F.H.)the Special Project for Enhancing Science and Technology Innovation Ability(frontier exploration)of Army Military Medical University(Third Military Medical University)(No.2019XQY12 to W.F.H.).
文摘Background:P311,a highly conserved 8 kDa intracellular protein,has recently been reported to play an important role in aggravating hypertrophic scaring by promoting the differentiation and secretion of fibroblasts.Nevertheless,how P311 regulates the differentiation and function of fibroblasts to affect granulation tissue formation remains unclear.In this work,we studied the underlying mechanisms via which P311 affects fibroblasts and promotes acute skin wound repair.Methods:To explore the role of P311,both in vitro and in vivo wound-healing models were used.Full-thickness skin excisional wounds were made in wild-type and P311−/−C57 adult mice.Wound healing rate,re-epithelialization,granulation tissue formation and collagen deposition were measured at days 3,6 and 9 after skin injury.The biological phenotypes of fibroblasts,the expression of target proteins and relevant signaling pathways were examined both in vitro and in vivo.Results:P311 could promote the proliferation and differentiation of fibroblasts,enhance the ability of myofibroblasts to secrete extracellular matrix and promote cell contraction,and then facilitate the formation of granulation tissue and eventually accelerate skin wound closure.Importantly,we discovered that P311 acts via up-regulating the expression of type II transforming growth factor-βreceptor(TGF-βRII)in fibroblasts and promoting the activation of the TGF-βRII-Smad signaling pathway.Mechanistically,the mammalian target of rapamycin signaling pathway is closely implicated in the regulation of the TGF-βRII-Smad pathway in fibroblasts mediated by P311.Conclusions:P311 plays a critical role in activation of the TGF-βRII-Smad pathway to promote fibroblast proliferation and differentiation as well as granulation tissue formation in the process of skin wound repair.
