Driving fibrosis in neuromuscular diseases: Role and regulation of Connective tissue growth factor (CCN2/CTGF)

Daniela L Rebolledo; Kenneth E Lipson; Enrique Brandan

doi:10.1016/j.mbplus.2021.100059

Driving fibrosis in neuromuscular diseases: Role and regulation of Connective tissue growth factor (CCN2/CTGF)

Matrix Biol Plus. 2021 Mar 6:11:100059. doi: 10.1016/j.mbplus.2021.100059. eCollection 2021 Aug.

Authors

Daniela L Rebolledo^{1

2}, Kenneth E Lipson³, Enrique Brandan^{1

4

5}

Affiliations

¹ Centro de Envejecimiento y Regeneración, CARE Chile UC, Chile.
² Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Punta Arenas, Chile.
³ FibroGen Inc., San Francisco, CA, USA.
⁴ Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile.
⁵ Fundación Ciencia y Vida, Santiago, Chile.

Abstract

Connective tissue growth factor or cellular communication network 2 (CCN2/CTGF) is a matricellular protein member of the CCN family involved in several crucial biological processes. In skeletal muscle, CCN2/CTGF abundance is elevated in human muscle biopsies and/or animal models for diverse neuromuscular pathologies, including muscular dystrophies, neurodegenerative disorders, muscle denervation, and muscle overuse. In this context, CCN2/CTGF is deeply involved in extracellular matrix (ECM) modulation, acting as a strong pro-fibrotic factor that promotes excessive ECM accumulation. Reducing CCN2/CTGF levels or biological activity in pathological conditions can decrease fibrosis, improve muscle architecture and function. In this work, we summarize information about the role of CCN2/CTGF in fibrosis associated with neuromuscular pathologies and the mechanisms and signaling pathways that regulate their expression in skeletal muscle.

Keywords: ALS, Amyotrophic Lateral Sclerosis; CCN2/CTGF; CCN2/CTGF, connective tissue growth factor; DMD, Duchenne muscular dystrophy; ECM, extracellular matrix; FG-3019; Fibrosis; LPA, lysophosphatidic acid; Neuromuscular diseases; Skeletal muscle.