Wang Jue, Shang Ruoyu, Yang Jiacai, Liu Zhihui, Chen Yunxia, Chen Cheng, Zheng Wenxia, Tang Yuanyang, Zhang Xiaorong, Hu Xiaohong, Huang Yong, Shen Han-Ming, Luo Gaoxing, He Weifeng
State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
Chongqing Key Laboratory for Disease Proteomics, Chongqing 400038, China.
Burns Trauma. 2022 Oct 13;10:tkac027. doi: 10.1093/burnst/tkac027. eCollection 2022.
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.
To explore the role of P311, both and 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 and .
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-β receptor (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.
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.
P311是一种高度保守的8 kDa细胞内蛋白，最近有报道称其通过促进成纤维细胞的分化和分泌在加重肥厚性瘢痕形成中发挥重要作用。然而，P311如何调节成纤维细胞的分化和功能以影响肉芽组织形成仍不清楚。在本研究中，我们探讨了P311影响成纤维细胞并促进急性皮肤伤口修复的潜在机制。
为了探究P311的作用，我们使用了体内和体外伤口愈合模型。在野生型和P311基因敲除的C57成年小鼠身上制作全层皮肤切除伤口。在皮肤损伤后第3、6和9天测量伤口愈合率、再上皮化、肉芽组织形成和胶原沉积。在体内和体外检测成纤维细胞的生物学表型、靶蛋白表达和相关信号通路。
P311可促进成纤维细胞的增殖和分化，增强肌成纤维细胞分泌细胞外基质的能力并促进细胞收缩，进而促进肉芽组织形成并最终加速皮肤伤口闭合。重要的是，我们发现P311通过上调成纤维细胞中II型转化生长因子-β受体（TGF-βRII）的表达并促进TGF-βRII-Smad信号通路的激活发挥作用。机制上，雷帕霉素靶蛋白信号通路与P311介导的成纤维细胞中TGF-βRII-Smad通路的调节密切相关。
P311在激活TGF-βRII-Smad通路以促进皮肤伤口修复过程中成纤维细胞增殖、分化以及肉芽组织形成方面起关键作用。
