Extracellular Matrix, Differentiation, and Fibrosis

We study the critical influence of the ECM on skeletal muscle differentiation. Our research investigates the interactions between myoblasts and their surrounding microenvironment, highlighting the crucial role of the extracellular matrix (ECM) in normal myogenesis. Disruptions in these interactions, particularly between the ECM and cellular receptors, impair muscle fiber formation. Furthermore, ECM interactions with fibroblasts modulate the expression of pro-fibrotic growth factors, such as connective tissue growth factor (CTGF/CCN2).

 Mechanisms of Fibrosis in Muscle Diseases

Fibrosis—marked by the excessive accumulation of ECM components—is a hallmark of skeletal muscle pathologies, including Duchenne muscular dystrophy (DMD), denervation, and motor neuron loss as seen in amyotrophic lateral sclerosis (ALS). Our work investigates the involvement of pro-fibrotic mediators, including transforming growth factor beta (TGF-β), connective tissue growth factor (CTGF/CCN2), and lysophosphatidic acid (LPA), in the development of muscle fibrosis. We also identify the specific cell populations responsible for the fibrotic response in various disease models. Additionally, we explore the contribution of the Hippo signaling pathway, focusing on its regulation of fibrotic factors and the mechanical properties, such as stiffness, of the skeletal muscle microenvironment. ​

Our overarching goal is to elucidate the role of the extracellular matrix (ECM) under both physiological and pathological conditions. Through this understanding, we aim to drive the development of novel therapeutic strategies for skeletal muscle disorders and to advance scientific knowledge in the field.