Taurine activates the AKT–mTOR axis to restore muscle mass and contractile strength in human 3D in vitro models of steroid myopathy

Abstract

Steroid myopathy is a clinically challenging condition exacerbated by prolonged corticosteroid use or adrenal tumors. In this study, we engineered a functional three-dimensional (3D) in vitro skeletal muscle model to investigate steroid myopathy. By subjecting our bioengineered muscle tissues to dexamethasone treatment, we reproduced the molecular and functional aspects of this disease. Dexamethasone caused a substantial reduction in muscle force, myotube diameter and induced fatigue. We observed nuclear translocation of the glucocorticoid receptor (GCR) and activation of the ubiquitin–proteasome system within our model, suggesting their coordinated role in muscle atrophy. We then examined the therapeutic potential of taurine in our 3D model for steroid myopathy. Our findings revealed an upregulation of phosphorylated AKT by taurine, effectively countering the hyperactivation of the ubiquitin–proteasomal pathway. Importantly, we demonstrate that discontinuing corticosteroid treatment was insufficient to restore muscle mass and function. Taurine treatment, when administered concurrently with corticosteroids, notably enhanced contractile strength and protein turnover by upregulating the AKT–mTOR axis. Our model not only identifies a promising therapeutic target, but also suggests combinatorial treatment that may benefit individuals undergoing corticosteroid treatment or those diagnosed with adrenal tumors.

The Extract of Gloiopeltis tenax Enhances Myogenesis and Alleviates Dexamethasone-Induced Muscle Atrophy

“…Taurine is water-soluble and has been found to be present in G. tenax in high concentrations [ 28 ]. It is known to play a positive role in skeletal muscle function by being involved in osmotic homeostasis, protein stability, oxidative stress, mitochondrial protein synthesis, and calcium homeostasis [ 29 , 30 ].…”

First person – Sheeza Mughal

“… ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping researchers promote themselves alongside their papers. Sheeza Mughal is first author on ‘ Taurine activates the AKT–mTOR axis to restore muscle mass and contractile strength in human 3D in vitro models of steroid myopathy ’, published in DMM. Sheeza is a PhD Student in the lab of Javier Ramón-Azcón at the Institute for Bioengineering of Catalonia (IBEC) in Barcelona, Spain, and is interested in developing disease models to simplify understanding of otherwise complex diseases.…”