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曾俊豪, 罗祖程, 陆瑶, 等. 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. DOI: 10.12025/j.issn.1008-6358.2024.20240093
引用本文: 曾俊豪, 罗祖程, 陆瑶, 等. 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. DOI: 10.12025/j.issn.1008-6358.2024.20240093
ZENG Junhao, LUO Zucheng, LU Yao, et al. The role of β2 adrenergic receptor in fibrogenesis during wound healing via TGF-β1/Smad3 signaling pathway[J]. Chinese Journal of Clinical Medicine, 2024, 31(2): 169-176. DOI: 10.12025/j.issn.1008-6358.2024.20240093
Citation: ZENG Junhao, LUO Zucheng, LU Yao, et al. The role of β2 adrenergic receptor in fibrogenesis during wound healing via TGF-β1/Smad3 signaling pathway[J]. Chinese Journal of Clinical Medicine, 2024, 31(2): 169-176. 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:
    目的 探讨β2肾上腺素受体(β2 adrenergic receptor, ADRB2)在创面愈合过程中对纤维增生的调控机制。
    方法 将12只小鼠背部皮肤随机注射非特异性敲减ADRB2基因的腺相关病毒(AAV-ADRB2组,n=6)和对照病毒(AAV-NC组,n=6)21 d后,在背部建立全层皮肤缺损创面愈合模型。记录术后第1、3、5、7天创面愈合率;采用H-E染色、Masson染色和免疫组化染色观察创面组织结构、纤维化程度及α-平滑肌肌动蛋白表达;定量PCR检测ADRB2、基质金属蛋白酶(matrix metalloproteinase, MMP)mRNA水平;Western印迹法检测胶原纤维1A1、胶原纤维3A1、TGF-β1、Smad3蛋白表达水平。
    结果 术后第5、7天,AAV-ADRB2组创面愈合率显著下降(P<0.05),伴随表皮增厚、炎症细胞增多、纤维细胞减少、胶原沉积降低;α-SMA水平显著下降(P<0.05);COL1A1/COL3A1比例减少(P<0.05);ADRB2 mRNA水平显著降低(P<0.01),MMP-1和MMP-8 mRNA水平升高(P<0.01);TGF-β1/Smad3蛋白水平显著下降(P<0.05)。
    结论 ADRB2敲减通过抑制TGF-β1/Smad3信号通路,减少创面纤维化反应和结缔组织含量,提高MMP mRNA水平,降低Ⅰ型/Ⅲ型胶原比例。

     

    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.

     

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