MiR-506-3p regulates autophagy and proliferation in post-burn skin fibroblasts through post-transcriptionally suppressin
- PDF / 1,615,895 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 88 Downloads / 117 Views
MiR-506-3p regulates autophagy and proliferation in post-burn skin fibroblasts through post-transcriptionally suppressing Beclin-1 expression Min Shi 1 & Xiaoming Zong 2 & Lei Chen 1 & Xiaobo Guo 3 & Xinqiang Ding 4 Received: 13 April 2020 / Accepted: 1 June 2020 / Editor: Tetsuji Okamoto # The Society for In Vitro Biology 2020
Abstract MicroRNAs (miRNAs) is involved in diverse biological processes of cells including dermal fibroblasts that contributed to wound healing and resulted in keloid scarring. MiR-506-3p has been identified as a tumor suppressor or oncogene in fibroblasts of various cancers, while the role of miR-506-3p in regulating functions of post-burn dermal fibroblasts is poorly known. In this study, miR506-3p was confirmed to be significantly downregulated in burned tissues and heat-stimulated dermal fibroblasts. Expression levels of autophagy-related proteins suggested thermal stimulus promoting the autophagy in dermal fibroblasts. Then, miR-506-3p inhibition enhanced cell proliferation and cell cycle process in dermal fibroblasts after thermal stimulus, whereas overexpression of miR-506-3p showed the opposite effect. Western blot assay showed that inhibition of miR-506-3p resulted in the upregulation of the expression levels of LC3-II, ATG5, and structural protein collagen I, as well as the downregulation of p62. Marker proteins of intermolecular cross-links in collagen synthesis, including hydroxylysylpyridinoline (HP), lysinepyridine (LP), and lysyl hydroxylase 2 (LH2), were increased by miR-506-3p overexpression and decreased by miR-506-3p inhibition. Moreover, transfection with miR-506-3p mimic suppressed the proliferation and autophagy in heat-stimulated dermal fibroblasts in a dose-dependent manner. Subsequently, dual luciferase reporter gene assay demonstrated that Beclin-1 was a direct target of miR-506-3p, and reintroduction of Beclin-1 could antagonize the suppressive effect of miR-506-3p overexpression on fibroblast proliferation, autophagy, and the intermolecular cross-links in collagen synthesis. Taken together, our findings showed that miR-506-3p regulated autophagy and proliferation in post-burn skin fibroblasts through post-transcriptionally suppressing Beclin-1 expression. Keywords Thermal injury . Dermal fibroblasts . Beclin-1 . miR-506-3p . Autophagy
Introduction Burn has become one of the most common forms of trauma, which induces increased metabolism and moisture loss and disturbs the immune system (Patil et al. 2017). Despite the
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11626-020-00472-3) contains supplementary material, which is available to authorized users. * Xinqiang Ding [email protected] 1
School of Medicine, Xi’an Peihua University, Xi’an, China
2
Department of Oncology, Shaanxi Friendship Hospital, Xi’an, China
3
Department of Hematology, Xi’an Central Hospital, Xi’an, China
4
Department of Dermatology, Xi’an Children’s Hospital, 69 Xijuyuan Road, Lianhu District, Xi’an 710000, China
advances in burn tr
Data Loading...
