A recent published in Cellular Physiology and Biochemistry examined the extent to which human fibro-adipogenic progenitor (FAP) proliferation, adipogenesis and fibrogenesis can be regulated by human myogenic progenitors (MPs) in physiological and pathological contexts.

In this study, FAPs and MPs were isolated from skeletal muscles of healthy young or old donors and Duchenne Muscular Dystrophy disease (DMD) patients. FAP/MP contact co-cultures and conditioned-media from undifferentiated MPs or differentiated myotubes were assessed on both, proliferation and fibro-adipogenic differentiation of FAPs.

The results showed that soluble molecules released by MPs activate the phosphoinositide 3-kinase (PI3Kinase)/Akt pathway in FAPs, resulting in the stimulation of FAP proliferation. While FAP differentiation was regulated by MP-derived myotubes through the secretion of pro-fibrogenic factors and anti-adipogenic factors. Notably, the regulation of FAP adipogenic and fibrogenic fates by myotubes was found to be mediated by Smad2 phosphorylation and the gene expression of glioma-associated oncogene homolog 1 (GLI1). However, regulations of proliferation and differentiation were disrupted for FAPs and MPs derived from aged individuals and patients with DMD.

The findings underscored a novel crosstalk between FAPs and the myogenic lineage in humans that could be crucial in the formation of adipocyte and myofibroblast accumulation in dystrophic and aged skeletal muscle.

Source: Cellular Physiology and Biochemistry. 2019;53(6):1029-1045. doi: 10.33594/000000196.