Sustained delivery of rhMG53 promotes diabetic wound healing and hair follicle development.
Sustained delivery of rhMG53 promotes diabetic wound healing and hair follicle development.
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DOI：
10.1016/j.bioactmat.2022.03.017
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发表时间：
2022-12
影响因子：
18.9
通讯作者：
Guan J
中科院分区：
文献类型：
--
作者：
Niu H;Li H;Guan Y;Zhou X;Li Z;Zhao SL;Chen P;Tan T;Zhu H;Bergdall V;Xu X;Ma J;Guan J
MG 53是细胞膜修复机制的重要组成部分，参与皮肤伤口的愈合。在这里，我们开发了一种新的递送系统，使用重组人MG 53（rhMG 53）蛋白和活性氧（ROS）清除凝胶治疗糖尿病伤口。MG 53消融的小鼠显示毛囊结构缺陷，局部应用rhMG 53可以促进mg 53 −/−小鼠的毛发生长。细胞谱系追踪研究揭示了MG 53在调节毛囊干细胞（HFSC）增殖中的生理功能。我们发现，rhMG 53保护HFSCs免受氧化应激诱导的凋亡，并刺激HFSCs分化为角质形成细胞。MG 53的细胞保护功能由HFSC中的STAT和MAPK信号传导介导。包封有rhMG 53的热敏ROS清除凝胶允许rhMG 53的持续释放，并促进db/db小鼠中慢性皮肤伤口的愈合和毛囊发育。这些发现支持了使用rhMG 53与ROS清除凝胶组合治疗糖尿病伤口的潜在治疗价值。MG 53的基因切除导致毛囊结构异常。MG 53能够增强毛囊干细胞在糖尿病伤口中存在的氧化应激条件下的存活和分化。MG 53的细胞保护作用是通过毛囊干细胞中的STATs和MAPK信号转导介导的。开发了一种水凝胶来逐渐释放rhMG 53、捕获伤口中的活性氧并提高氧化应激下毛囊干细胞的存活率。rhMG 53/水凝胶的递送加速db/db小鼠中的伤口闭合和毛囊发育。
MG53 is an essential component of the cell membrane repair machinery, participating in the healing of dermal wounds. Here we develop a novel delivery system using recombinant human MG53 (rhMG53) protein and a reactive oxygen species (ROS)-scavenging gel to treat diabetic wounds. Mice with ablation of MG53 display defective hair follicle structure, and topical application of rhMG53 can promote hair growth in the mg53−/− mice. Cell lineage tracing studies reveal a physiological function of MG53 in modulating the proliferation of hair follicle stem cells (HFSCs). We find that rhMG53 protects HFSCs from oxidative stress-induced apoptosis and stimulates differentiation of HSFCs into keratinocytes. The cytoprotective function of MG53 is mediated by STATs and MAPK signaling in HFSCs. The thermosensitive ROS-scavenging gel encapsulated with rhMG53 allows for sustained release of rhMG53 and promotes healing of chronic cutaneous wounds and hair follicle development in the db/db mice. These findings support the potential therapeutic value of using rhMG53 in combination with ROS-scavenging gel to treat diabetic wounds. Genetic ablation of MG53 led to abnormal hair follicle structure. MG53 was able to enhance hair follicle stem cell survival and differentiation under oxidative stress condition existing in diabetic wounds. The cytoprotective function of MG53 was mediated by STATs and MAPK signaling in hair follicle stem cells. A hydrogel was developed to gradually release rhMG53, capture ROS in wounds, and improve hair follicle stem cell survival under oxidative stress. Delivery of rhMG53/hydrogel accelerated wound closure and hair follicle development in db/db mice.
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影响因子：
13.6
作者：
Guan Y;Niu H;Liu Z;Dang Y;Shen J;Zayed M;Ma L;Guan J
通讯作者：
Guan J
影响因子：
4.6
作者：
Bigarella, Carolina L.;Liang, Raymond;Ghaffari, Saghi
通讯作者：
Ghaffari, Saghi
影响因子：
17.1
作者：
Duann P;Li H;Lin P;Tan T;Wang Z;Chen K;Zhou X;Gumpper K;Zhu H;Ludwig T;Mohler PJ;Rovin B;Abraham WT;Zeng C;Ma J
通讯作者：
Ma J
DOI：
10.1109/access.2023.3293001
发表时间：
--
期刊：
IEEE Access
影响因子：
3.6
作者：
Yi-Ming Tseng; Bang-Ren Chen; Wei-Cheng Lin; Wen-Jay Lee; Nan-Yow Chen; Tian-Li Wu
通讯作者：
Yi-Ming Tseng
影响因子：
4.6
作者：
Anjum F;Agabalyan NA;Sparks HD;Rosin NL;Kallos MS;Biernaskie J
通讯作者：
Biernaskie J