FAPs orchestrate homeostasis of muscle physiology and pathophysiology

Abstract

As a common clinical manifestation, muscle weakness is prevalent in people with mobility disorders. Further studies of muscle weakness have found that patients with muscle weakness present with persistent muscle inflammation, loss of muscle fibers, fat infiltration, and interstitial fibrosis. Therefore, we propose the concept of muscle microenvironment homeostasis, which explains the abnormal pathological changes in muscles through the imbalance of muscle microenvironment homeostasis. And we identified an interstitial progenitor cell FAP during the transition from normal muscle microenvironment homeostasis to muscle microenvironment imbalance caused by muscle damage diseases. As a kind of pluripotent stem cell, FAPs do not participate in myogenic differentiation, but can differentiate into fibroblasts, adipocytes, osteoblasts, and chondrocytes. As a kind of mesenchymal progenitor cell, it is involved in the generation of extracellular matrix, regulate muscle regeneration, and maintain neuromuscular junction. However, the muscle microenvironment is disrupted by the causative factors, and the abnormal activities of FAPs eventually contribute to the complex pathological changes in muscles. Targeting the mechanisms of these muscle pathological changes, we have identified appropriate signaling targets for FAPs to improve and even treat muscle damage diseases. In this review, we propose the construction of muscle microenvironmental homeostasis and find the key cells that cause pathological changes in muscle after homeostasis is broken. By studying the mechanism of abnormal differentiation and apoptosis of FAPs, we found a strategy to inhibit the abnormal pathological changes in muscle damage diseases and improve muscle regeneration.