Endoplasmic Reticulum Stress Induces Myostatin High Molecular Weight Aggregates and Impairs Mature Myostatin Secretion.

ABSTRACT: Sporadic inclusion body myositis (sIBM) is the most prevalent acquired muscle disorder in the elderly with no defined etiology or effective therapy. Endoplasmic reticulum stress and deposition of myostatin, a secreted negative regulator of muscle growth, have been implicated in disease pathology. The myostatin signaling pathway has emerged as a major target for symptomatic treatment of muscle atrophy. Here, we systematically analyzed the maturation and secretion of myostatin precursor MstnPP and its metabolites in a human muscle cell line. We find that increased MsntPP protein levels induce ER stress. MstnPP metabolites were predominantly retained within the endoplasmic reticulum (ER), also evident in sIBM histology. MstnPP cleavage products formed insoluble high molecular weight aggregate

SUBMITTER: Sachdev R 

PROVIDER: S-EPMC6153721 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature