• Burns · May 2024

    Exogenous PRAS40 reduces KLF4 expression and alleviates hypertrophic scar fibrosis and collagen deposition through inhibiting mTORC1.

    • Chao Wang and Duyin Jiang.
    • Department of Burn and Plastic Surgery, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China.
    • Burns. 2024 May 1; 50 (4): 936946936-946.

    BackgroundTo identify the anti-fibrosis effect of PRAS40 in scar, and its potential mechanism.MethodsWe constructed a rat model of hypertrophic scarthat was locally injected the PRAS40 overexpression adenoviruses, mTORC1 inhibitor MHY1485 and activator rapamycin, and further observed the pathological changes of skin tissue and the severity of fibrosis by HE, Masson and sirius red staining, and analyzed the deposition of a-SMA and collagen I by western blot and immunofluorescence test. Meanwhile, the co-localization of KLF4 with a-SMA and type I collagen was analyzed, as well as the regulatory effect of PRAS40 on KLF4. In addition, we also verified whether the inhibition of scar fibrosis by PRAS40 is related to mTORC1, and whether the upregulation of KLF4 is related to mTORC1.ResultsThe results showed that the expression of PRAS40 was low and p-PRAS40 was high in scar skin tissue. After local injection of PRAS40 overexpression adenovirus, the expression of PRAS40 in skin tissue was increased. The overexpression of PRAS40 can inhibit scar skin fibrosis and reduce the content of a-SMA and collagen I. Further mechanism analysis confirms that the inhibitory effect of PRAS40 on skin fibrosis is related to mTORC1, and PRAS40 inhibits the activation of mTORC1. The expression of KLF4 is relatively low in scar tissue. PRAS40 administration upregulated the expression of KLF4, which is related to mTORC1 CONCLUSIONS: PRAS40 significantly improves fibrosis of scar skin tissue and increases the expression of KLF4 in scars. The anti-fibrotic effect of PRAS40 depends on mTORC1.Copyright © 2024 Elsevier Ltd and ISBI. All rights reserved.

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