Journal article
Expression profile and overexpression outcome indicate a role for beta Klotho in skeletal muscle fibro/adipogenesis
The FEBS journal, Vol.283(9), pp.1653-1668
05/2016
PMID: 26881702
Abstract
Regeneration of skeletal muscles is required throughout life to ensure optimal performance. Therefore, a better understanding of the resident cells involved in muscle repair is essential. Muscle repair relies on satellite cells (SCs), the resident myogenic progenitors, but also involves the contribution of interstitial cells including fibro/adipocyte progenitors (FAPs). To elucidate the role of the fibroblast growth factor (FGF) signaling in these two cell populations, we previously analyzed freshly isolated cells for their FGF receptor (FGFR) signature. Transcript analysis of the four Fgfr genes revealed distinct expression profiles for SCs and FAPs, raising the possibility that these two cell types have different FGF-mediated processes. Here, we pursued this hypothesis exploring the role of the Klotho genes, whose products are known to function as FGFR co-receptors for the endocrine FGF subfamily. Isolated SC and FAP populations were analyzed in culture, exhibiting spontaneous myogenic or adipogenic differentiation, respectively. alpha Klotho expression was not detected in either population. beta Klotho expression, while not detected in SCs, was strongly upregulated in FAPs entering adipogenic differentiation, coinciding with expression of a panel of adipogenic genes and preceding the appearance of intracellular lipid droplets. Overexpression of beta Klotho in mouse cell line models enhanced adipogenesis in NIH3T3 fibroblasts but had no effect on C2C12 myogenic cells. Our study supports a pro-adipogenic role for beta Klotho in skeletal muscle fibro/adipogenesis and calls for further research on involvement of the FGF-FGFR-beta Klotho axis in the fibro/adipogenic infiltration associated with functional deterioration of skeletal muscle in aging and muscular dystrophy.
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Details
- Title
- Expression profile and overexpression outcome indicate a role for beta Klotho in skeletal muscle fibro/adipogenesis
- Creators
- Michael Phelps - University of WashingtonPascal Stuelsatz - University of WashingtonZipora Yablonka-Reuveni - University of Washington
- Publication Details
- The FEBS journal, Vol.283(9), pp.1653-1668
- Academic Unit
- Department of Animal Sciences
- Publisher
- Wiley
- Number of pages
- 16
- Grant note
- AG021566; NS090051; AG035377; NS088804 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 18574 / AFM-telethon fellowship T32AG000057 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) R21NS090051 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) T32 AG000057 / Genetic Approaches to Aging Training Program
- Identifiers
- 99901397957901842
- Language
- English
- Resource Type
- Journal article