Description

Dr. Harry Karmouty-Quintana, Associate Professor in the Department of Biochemistry and Molecular Biology at McGovern Medical School, UT Health Houston, will present his talk entitled, "Sugar-coated scars: Hyaluronan remodeling of the lung matrix in pulmonary hypertension."

Abstract: Pulmonary hypertension (PH), a progressive vascular disease that is commonly present in chronic lung conditions such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). A hallmark of PH is vascular remodeling, yet the role of extracellular matrix dynamics in this process is not fully defined. Hyaluronan (HA), a matrix glycan elevated in IPF, COPD, and PH, is a key contributor to this remodeling. We identify pulmonary artery smooth muscle cells (PASMCs) as a central source of HA overproduction in PH, driven by 3'UTR shortening of HAS2 following loss of NUDT21, a regulator of alternative polyadenylation. This dysregulation leads to mitochondrial dysfunction and a in PASMCs, promoting proliferation, migration, and increased contractility. Mice overexpressing HAS2 in smooth muscle develop spontaneous PH, while genetic deletion or pharmacologic inhibition of HAS2 restores mitochondrial function and reverses disease features. These findings reveal a shared HA-driven mechanism linking chronic lung disease to PH pathogenesis.