Inactivation of Beclin-1-dependent autophagy promotes ursolic acid-induced apoptosis in hypertrophic scar fibroblasts.

Inactivation of Beclin-1-dependent autophagy promotes ursolic acid-induced apoptosis in hypertrophic scar fibroblasts.

Exp Dermatol. 2017 Aug 02;:

Authors: Cao C, Wang W, Lu L, Wang L, Chen X, Guo R, Li S, Jiang J

Abstract
A hypertrophic scar (HS) is caused by abnormal proliferation of dermal fibroblasts. Thus, promoting hypertrophic scar fibroblast (HSFB) apoptosis is an effective strategy for HS therapy. Ursolic acid (UA) has been widely used as an inducer of apoptosis in diverse cancers. However, whether UA plays an inhibitory role in HS formation is still unknown. In our study, UA was used to treat HSFBs and the cell viability, apoptosis, and collagen synthesis were determined by a Cell Counting Kit 8 (CCK8) assay, flow cytometry, and an H(3) -proline incorporation assay, respectively. Autophagy activity was detected by LC3 immunoblotting and electron microscopy, and siRNAs targeting Beclin-1 were used to inhibit autophagy. Western blotting was performed to investigate the molecular changes in HSFBs after various treatments. We found that UA inhibited collagen synthesis and induced cell apoptosis in HSFBs, evidenced by the deregulated expression of Bim, Bcl-2 and Cyto C. Furthermore, we demonstrated that US induced autophagy and inactivation of autophagy promoted UA-induced apoptosis and collagen synthesis inhibition in HSFBs. Molecular investigation indicated that UA induced autophagy through upregulation of Beclin-1 and knockdown of Beclin-1 prevent UA-induced autophagy. Overexpression of Bcl-2 prevent UA-induced autophagy, Beclin-1 upregulation, apoptosis and collagen synthesis inhibition in HSFBs. Collectively, our study demonstrated that UA is a novel agent for inhibiting HS formation by promoting apoptosis, especially in combination with an autophagy inhibitor. Our results provide strong evidence of the application of UA in clinical HS treatment. This article is protected by copyright. All rights reserved.

PMID: 28767174 [PubMed - as supplied by publisher]

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