Translational research : the journal of laboratory and clinical medicine
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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. ⋯ 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.
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Angiopoietin-like protein 8 (ANGPTL8), a protein implicated in lipid and glucose homeostasis, is present only in mammals, suggesting that it is involved in processes unique to these vertebrates such as pregnancy and homeothermy. We explored the role of ANGPTL8 in maternal-fetal crosstalk and its relationship with newborn adiposity. In a longitudinal analysis of healthy pregnant women, ANGPTL8 levels decreased progressively during pregnancy although remained higher than levels in the postpartum period. ⋯ Studies in vitro revealed that ANGPTL8 was secreted by brown adipocytes and its expression was increased in experimental models of white-to-brown fat conversion. In addition, ANGPTL8 induced the expression of markers of brown adipocytes. The high levels of ANGPTL8 found in fetal life together with its relationship with newborn adiposity and brown adipose tissue point to ANGPTL8 as a potential new player in the modulation of the thermogenic machinery during the fetal-neonatal transition.