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Development. 2016 Nov 15;143(22):4137-4148. Epub 2016 Oct 5.

MicroRNA deep sequencing in two adult stem cell populations identifies miR-501 as a novel regulator of myosin heavy chain during muscle regeneration.

Author information

1
Division of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital Zurich, Zurich 8091, Switzerland.
2
Competence Center Personalized Medicine UZH/ETH, ETH Zurich and University of Zurich, Zurich, Switzerland.
3
Institute of Neuropathology, University Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
4
Division of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital Zurich, Zurich 8091, Switzerland jan.kruetzfeldt@usz.ch.
5
Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.

Abstract

MicroRNAs (miRNAs) are important regulators of skeletal muscle regeneration, but the underlying mechanisms are still incompletely understood. Here, comparative miRNA sequencing analysis of myogenic progenitor cells (MPs) and non-myogenic fibroblast-adipocyte progenitors (FAPs) during cardiotoxin (CTX)-induced muscle injury uncovered miR-501 as a novel muscle-specific miRNA. miR-501 is an intronic miRNA and its expression levels in MPs correlated with its host gene, chloride channel, voltage-sensitive 5 (Clcn5). Pharmacological inhibition of miR-501 dramatically blunted the induction of embryonic myosin heavy chain (MYH3) and, to a lesser extent, adult myosin isoforms during muscle regeneration, and promoted small-diameter neofibers. An unbiased target identification approach in primary myoblasts validated gigaxonin as a target of miR-501 that mimicked the effect of miR-501 inhibition on MYH3 expression. In the mdx mouse model, which models a pathological disease state, not only was miR-501 induced in regenerating skeletal muscle, but also its serum levels were increased, which correlated with the disease state of the animals. Our results suggest that miR-501 plays a key role in adult muscle regeneration and might serve as a novel serum biomarker for the activation of adult muscle stem cells.

KEYWORDS:

MicroRNA; Myosin; Regeneration; Serum; Skeletal muscle

PMID:
27707793
PMCID:
PMC5117213
DOI:
10.1242/dev.136051
[Indexed for MEDLINE]
Free PMC Article

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