Syndecan-4–/– Mice Have Smaller Muscle Fibers, Increased Akt/mTOR/S6K1 and Notch/HES-1 Pathways, and Alterations in Extracellular Matrix Components

Frontiers in Cell and Developmental Biology

Jan Magnus Aronsen¹  Addolorata Pisconti²  Svein Olav Kolset³  Kristian Hovde Liland⁴  Cathrine Rein Carlson⁵  Marianne Lunde⁵  Ivar Sjaastad⁶  Geir Christensen⁶  Vibeke Høst⁷  Sissel Beate Rønning⁷  Mona Elisabeth Pedersen⁷ 

[1]Bjørknes College, Oslo, Norway

[2]Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, United States

[3]Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

[4]Faculty of Sciences and Technology, Norwegian University of Life Sciences, Ås, Norway

[5]Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway

[6]K.G. Jebsen Center for Cardiac Research, University of Oslo, Oslo, Norway

[7]Nofima AS, Ås, Norway

关键词: skeletal muscle;    syndecan;    exercise;    myogenesis;    Notch;    decorin;   

DOI  :  10.3389/fcell.2020.00730

来源: DOAJ

【 摘 要 】

BackgroundExtracellular matrix (ECM) remodeling is essential for skeletal muscle development and adaption in response to environmental cues such as exercise and injury. The cell surface proteoglycan syndecan-4 has been reported to be essential for muscle differentiation, but few molecular mechanisms are known. Syndecan-4–/– mice are unable to regenerate damaged muscle, and display deficient satellite cell activation, proliferation, and differentiation. A reduced myofiber basal lamina has also been reported in syndecan-4–/– muscle, indicating possible defects in ECM production. To get a better understanding of the underlying molecular mechanisms, we have here investigated the effects of syndecan-4 genetic ablation on molecules involved in ECM remodeling and muscle growth, both under steady state conditions and in response to exercise.MethodsTibialis anterior (TA) muscles from sedentary and exercised syndecan-4–/– and WT mice were analyzed by immunohistochemistry, real-time PCR and western blotting.ResultsCompared to WT, we found that syndecan-4–/– mice had reduced body weight, reduced muscle weight, muscle fibers with a smaller cross-sectional area, and reduced expression of myogenic regulatory transcription factors. Sedentary syndecan-4–/– had also increased mRNA levels of syndecan-2, decorin, collagens, fibromodulin, biglycan, and LOX. Some of these latter ECM components were reduced at protein level, suggesting them to be more susceptible to degradation or less efficiently translated when syndecan-4 is absent. At the protein level, TRPC7 was reduced, whereas activation of the Akt/mTOR/S6K1 and Notch/HES-1 pathways were increased. Finally, although exercise induced upregulation of several of these components in WT, a further upregulation of these molecules was not observed in exercised syndecan-4–/– mice.ConclusionAltogether our data suggest an important role of syndecan-4 in muscle development.

【 授权许可】

Unknown