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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