中国临床医学2024，Vol.31Issue(2)：169-176,8.DOI:10.12025/j.issn.1008-6358.2024.20240093
β2肾上腺素受体通过TGF-β1/Smad3信号通路调控创面愈合中的纤维增生
The role of β2 adrenergic receptor in fibrogenesis during wound healing via TGF-β1/Smad3 signaling pathway
摘要
Abstract
Objective To explore the underlying mechanism of β2 adrenergic receptor(ADRB2)in fibrogenesis during wound healing.Methods Non-specific ADRB2 gene knockdown adeno-associated virus(AAV-ADRB2 group,6 mice)and control virus(AAV-NC group,6 mice)was injected randomly into the back skin of 12 mice for 21 days,a full-thickness skin defected wound healing murine model was established.Wound healing rates were recorded at the 1st,3rd,5th,and 7th day after operation.Histological examinations by H-E staining,Masson staining,and immunohistochemistry were conducted to observe wounded skin tissue structure,fibrosis,and α-SMA protein expression;quantitative PCR was employed to analyze ADRB2 and matrix metalloproteinase(MMP)mRNA levels;Western blotting was utilized to assess the protein expression levels of COL1A1,COL3A1,TGF-β1,and Smad3.Results On postoperative day 5 and 7,the wound healing rate of the AAV-ADRB2 group significantly decreased(P＜0.05),accompanied by a series pathological changes,including thickened epidermis,exaggerated inflammation,reduced fibroblast count,and inhibited collagen deposition;the α-SMA expression showed a significant decrease(P＜0.05),and the ratio of COL1A1 to COL3A1 decreased(P＜0.05);ADRB2 mRNA levels significantly decreased(P＜0.01),while MMP-1 and MMP-8 mRNA levels increased(P＜0.01);the protein levels of TGF-β1 and Smad3 exhibited a significant decrease(P＜0.05).Conclusions ADRB2 knockdown reduced fibrosis during wound healing and degenerated connective tissue content around the wound bed by inhibiting the TGF-β1/Smad3 signaling pathway,which leads to an increase in MMP mRNA levels and a decrease in the ratio of type Ⅰ to type Ⅲ collagen.关键词
β2肾上腺素受体/TGF-β1/Smad3信号通路/创面愈合/纤维增生Key words
β2 adrenergic receptor/TGF-β1/Smad3 signaling pathway/wound healing/fibrogenesis分类
医药卫生引用本文复制引用
曾俊豪,罗祖程,陆瑶,栾文杰,亓发芝..β2肾上腺素受体通过TGF-β1/Smad3信号通路调控创面愈合中的纤维增生[J].中国临床医学,2024,31(2):169-176,8.基金项目
国家自然科学基金(82172212,82372518).Supported by National Nature Science Foundation of China(82172212,82372518). （82172212,82372518）
