miR-23b promotes cutaneous wound healing through inhibition of the inflammatory responses by targeting ASK1.

Wound healing is a complicated event that develops in three overlapping phases: inflammatory, proliferative, and remodeling. MicroRNAs (miRNAs) have been proved to play an important role in the healing process of skin trauma, and alteration of specific miRNA expression during different phases may be associated with abnormal wound healing. In this study, we determined the variation of miR-23b expression after trauma in normal mice and in cultured cells exposed to lipopolysaccharide. We further demonstrated that excessive miR-23b could significantly accelerate wound healing in vivo. Up-regulation of miR-23b decreases infiltration of inflammatory cells, as evidenced by pathologic staining. Meanwhile, miR-23b could significantly inhibit the expression of pro-inflammatory cytokines, including TNF-α, IL-1ß, IL-6, and Ccl2, and significantly increase anti-inflammatory factor IL-10. Furthermore, miR-23b could also promote α-SMA expression in a fiber pattern and increase the expression of Col1a1 and Col3a1. Importantly, we also showed that miR-23b could inhibit inflammation to promote wound healing by targeting apoptotic signal-regulating kinase 1 (ASK1). Notably, knockdown of ASK1 could reduce inflammation factor expression in vitro. Together, our data reveal that miR-23b is a potent therapeutic agent for cutaneous wound healing that shortens the period of inflammatory responses and promotes keratinocyte migration for the re-epithelialization of wound sites.

Alteration in microRNA-25 expression regulate cardiac function via renin secretion.

Heart failure arises from diverse cardiovascular diseases, including hypertension, ischemic disease and atherosclerosis, valvular insufficiency, myocarditis, and contractile protein mutations. MicroRNAs are dysregulated in heart failure, but identification of the specific microRNAs involved remains incomplete. Here, we evaluate miR-25 expression in the peripheral blood from healthy, dilated cardiomyopathy (DCM), remote infarct (OMI), hypertensive heart disease (HHD), and HHD resulting in heart failure (HHDF) using q-PCR. Interestingly, we discovered miR-25 expression in humans is initially decreased at the onset of heart failure but is later increased in end-stage heart failure. We also show that overexpression of miR-25 in normal mice causes cardiomyocyte fibrosis and apoptosis. However, inhibition of miR-25 in normal mice led to activate renin-angiotensin system (RAS) and high blood pressure, mild heart dilation. Notably, the miR-25 cluster knock-out mice was also characterized high blood pressure and no obvious cardiac function alteration. RNA sequencing showed the alteration of miR-25 target genes in angomir-treated mice, including the renin secretion signal related gene. In vitro, cotransfection with the miR-25 antagomir repressed luciferase activity from a reporter construct containing the Pde3a and Cacnalc untranslated region. In summary, miR-25 expression during different stages of heart disease, offers a new perspective for the role of miR-25 function in heart failure.