Inhibition of microRNA‐92a increases blood vessels and satellite cells in skeletal muscle but does not improve duchenne muscular dystrophy–related phenotype in mdx mice

Abstract

Introduction: The vasculature and blood flow in muscle are perturbed in Duchenne muscular dystrophy (DMD) and its mdx mouse model. MicroRNA‐92a (miR‐92a) is enriched in endothelial cells, especially during ischemic injury. Methods: Because antagonizing miR‐92a was shown to result in increased proliferation and migration of endothelial cells and recovery from ischemia, we assessed the effects of Antagomir‐92a in vitro in muscle stem cell culture and in vivo in mdx mice. Results: miR‐92a was found to be highly expressed in muscle endothelial cells and satellite cells. Treatment with Antagomir‐92a increased capillary density and tissue perfusion, which was accompanied by an increase in satellite cells. However, Antagomir‐92a–treated mdx mice showed no histological improvement and had worse muscle function. Antagomir‐92a suppressed myogenic differentiation in satellite cell culture. Discussion: AntagomiR‐92a improves the vasculature but not the muscle in mdx mice, possibly due to its side effects on satellite cell differentiation. Muscle Nerve 59:594–594, 2019

Assessment of the Diagnostic Potential of miR-29a-3p and miR-92a-3p as Circulatory Biomarkers in Acute Myeloid Leukemia

“…family is a central epigenetic regulators that showed to have a significant role as anti-tumorigenic molecules in different forms of cancer (Iqbal et al, 2012;Tari et al, 2018). Additionally, miR-92a plays a crucial role in the growth of human organs such as heart (Wong et al, 2016), lungs (Zhu et al, 2018) and immune system (Liang et al, 2016) but also the formation of blood vessels (Verma et al, 2019). The circulating levels of mir-92a was found to be elevated in the liver tissue of patients with hepatocellular carcinoma (Shigoka et al, 2010), while low levels of mir-92a were correlated with multiple myeloma (Yoshizawa et al, 2012).…”

Muscle and cardiac therapeutic strategies for Duchenne muscular dystrophy: past, present, and future

“…On the other hand, we have found that miR-146a, known to diminish inflammation and fibrosis in different tissues by downregulating the expression of proinflammatory cytokines, does not significantly affect the deleterious pathological events of DMD progression in mdx mice [ 224 ]. Another study pointed out the lack of beneficial effect of miR-92a inhibition on DMD progression in mdx mice despite the increased capillary density and tissue perfusion that was found after antagomir-92a [ 270 ].…”

Tissue engineering modalities in skeletal muscles: focus on angiogenesis and immunomodulation properties

“…Skeletal muscles are consolidated tissue and consist of aligned multinucleated myocytes, satellite cells, nerves, blood vessels, and extracellular matrix (ECM) in complex structures [ 1 – 3 ]. Like other tissues, skeletal muscles are sensitive to varied acute and chronic injuries caused by physical trauma, plastic/cosmetic surgeries, arterial occlusion, metabolic diseases, peripheral nerve atrophies, congenital diseases, etc.…”