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Inactivation of Beclin‐1‐dependent autophagy promotes ursolic acid‐induced apoptosis in hypertrophic scar fibroblasts
Author(s) -
Cao Chuan,
Wang Wenping,
Lu Lele,
Wang Liang,
Chen XiaoSong,
Guo Rui,
Li Shirong,
Jiang Junzi
Publication year - 2018
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13410
Subject(s) - autophagy , ursolic acid , hypertrophic scar , apoptosis , microbiology and biotechnology , chemistry , biology , biochemistry , anatomy , chromatography
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 HSFB s and the cell viability, apoptosis, and collagen synthesis were determined by a Cell Counting Kit 8 assay, flow cytometry, and an H 3 ‐proline incorporation assay, respectively. Autophagy activity was detected by LC 3 immunoblotting and electron microscopy, and si RNA s targeting Beclin‐1 were used to inhibit autophagy. Western blotting was performed to investigate the molecular changes in HSFB s after various treatments. We found that UA inhibited collagen synthesis and induced cell apoptosis in HSFB s, evidenced by the deregulated expression of Bim, Bcl‐2 and Cyto C. Furthermore, we demonstrated that UA induced autophagy and inactivation of autophagy promoted UA ‐induced apoptosis and collagen synthesis inhibition in HSFB s. 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 prevents UA ‐induced autophagy, Beclin‐1 upregulation, apoptosis and collagen synthesis inhibition in HSFB s. 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.