title: Age-related changes in miR-143-3p:Igfbp5 interactions affect muscle regeneration.
abstract: A common characteristic of aging is defective regeneration of skeletal muscle. The molecular pathways underlying age-related decline in muscle regenerative potential remain elusive. microRNAs are novel gene regulators controlling development and homeostasis and the regeneration of most tissues, including skeletal muscle. Here, we use satellite cells and primary myoblasts from mice and humans and an in vitro regeneration model, to show that disrupted expression of microRNA-143-3p and its target gene, Igfbp5, plays an important role in muscle regeneration in vitro. We identified miR-143 as a regulator of the insulin growth factor-binding protein 5 (Igfbp5) in primary myoblasts and show that the expression of miR-143 and its target gene is disrupted in satellite cells from old mice. Moreover, we show that downregulation of miR-143 during aging may act as a compensatory mechanism aiming at improving myogenesis efficiency; however, concomitant upregulation of miR-143 target gene, Igfbp5, is associated with increased cell senescence, thus affecting myogenesis. Our data demonstrate that dysregulation of miR-143-3p:Igfbp5 interactions in satellite cells with age may be responsible for age-related changes in satellite cell function.
authors.affiliation: Institute of Ageing and Chronic Disease, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Soriano-Arroquia
authors.affiliation: Institute of Ageing and Chronic Disease, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: McCormick
authors.affiliation: University Hospital Aintree, Liverpool, UK.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Molloy
authors.affiliation: Institute of Ageing and Chronic Disease, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: McArdle
authors.affiliation: Institute of Ageing and Chronic Disease, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Goljanek-Whysall
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016922:Cellular Senescence / Q000502:physiology; D005260:Female; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C000607595:IGFBP5-interacting protein, mouse; D018975:Insulin-Like Growth Factor Binding Protein 5; C555159:MIRN142 microRNA, human; D035683:MicroRNAs; C532884:MIRN143 microRNA, mouse
keywords: aging; microRNA; muscle; regeneration; sarcopenia; senescence