Non-Glycanated Biglycan and LTBP4: Leveraging the extracellular matrix for Duchenne Muscular Dystrophy therapeutics

Matrix Biology : Journal of the International Society for Matrix Biology
Justin R Fallon, Elizabeth M McNally

Abstract

The extracellular matrix (ECM) plays key roles in normal and diseased skeletal and cardiac muscle. In healthy muscle the ECM is essential for transmitting contractile force, maintaining myofiber integrity and orchestrating cellular signaling. Duchenne Muscular Dystrophy (DMD) is caused by loss of dystrophin, a cytosolic protein that anchors a transmembrane complex and serves as a vital link between the actin cytoskeleton and the basal lamina. Loss of dystrophin leads to membrane fragility and impaired signaling, resulting in myofiber death and cycles of inflammation and regeneration. Fibrosis is also a cardinal feature of DMD. In this review, we will focus on two cases where understanding the normal function and regulation of ECM in muscle has led to the discovery of candidate therapeutics for DMD. Biglycan is a small leucine rich repeat ECM protein present as two glycoforms in muscle that have dramatically different functions. One widely expressed form is biglycan proteoglycan (PG) that bears two chondroitin sulfate GAG chains (typically chondroitin sulfate) and two N-linked carbohydrates. The second glycoform, referred to as 'NG' (non-glycanated) biglycan, lacks the GAG side chains. NG, but not PG biglycan recruits utrophin, ...Continue Reading

Citations

Sep 15, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jennifer M PetrosinoFederica Accornero
Oct 11, 2019·Connective Tissue Research·Patricia A Miguez
Jul 7, 2020·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Jinyang Zeng-BrouwersLiliana Schaefer
Jul 30, 2020·Annals of the New York Academy of Sciences·Obiajulu AghaBrian T Feeley
Feb 23, 2020·Frontiers in Pharmacology·Tanaya Walimbe, Alyssa Panitch
Jul 9, 2020·International Journal of Molecular Sciences·Ting-Yi LinJong-Hau Hsu
Jun 29, 2021·Molecular and Cellular Biochemistry·Sandeep AppunniAlpana Sharma

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.