کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5685115 1597932 2016 22 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Overexpression of miR-29b reduces collagen biosynthesis by inhibiting heat shock protein 47 during skin wound healing
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی پزشکی و دندانپزشکی (عمومی)
پیش نمایش صفحه اول مقاله
Overexpression of miR-29b reduces collagen biosynthesis by inhibiting heat shock protein 47 during skin wound healing
چکیده انگلیسی
Skin scar formation is characterized by excessive synthesis and aberrant deposition of collagens during wound healing. MicroRNAs are endogenous gene regulators critically involved in diverse biological events including skin scar formation and hold considerable promise as therapeutic targets. However, the detailed molecular mechanisms responsible for collagen production during skin wound repair and scar formation remain incompletely known. Here our data revealed that significant downregulation of miR-29b and upregulation of heat shock protein 47 (HSP47) were observed during wound healing in both excisional and burn wound models and also detected in facial skin scar as compared to adjacent healthy skin. HSP47, a specific chaperon for collagen production and secretion, was identified as a novel and direct post-transcriptional target of miR-29b in skin fibroblasts via bioinformatics prediction and experimental validation. Moreover, the regulatory functions of miR-29b in collagen biosynthesis are partially achieved through modulating HSP47 expression in skin fibroblasts. Furthermore, the profibrotic growth factor TGF-β1 inhibited miR-29b transcription by activating TGF-β/Smads signaling and in turn depressed HSP47 and enhanced collagen 1 production. In contrast, the proinflammatory cytokines IL-1β and TNF-α significantly induced miR-29b transcription via activating NF-κB signaling but had no significant effect on HSP47 and collagen production in skin fibroblasts. Importantly, local delivery of miR-29b lentiviral particles inhibited HSP47 expression and collagen biosynthesis as well as suppressed angiogenesis, thus reducing scar formation in an excisional wound splinting model. Collectively, our data reveal that miR-29b can reduce collagen biosynthesis during skin wound healing likely via post-transcriptional inhibition of HSP47 expression. These findings also suggest that therapeutic targeting of miR-29b/HSP47 might be a viable alternative strategy to prevent or reduce scar formation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Translational Research - Volume 178, December 2016, Pages 38-53.e6
نویسندگان
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