Scott D. Collum, Lisha Zhu, Tingting W. Mills, Rene Girard, Jamie Tran, Tinne C. J. Mertens, Cory Wilson, Nancy Wareing, Erik E. Suarez, Howard J. Huang, Rahat Hussain, Bindu Akkanti, Wenjin J. Zheng, Hari K. Yalamanchili, Bela Patel, Eric J. Wagner, Sandeep Agarwal, Harry Karmouty-Quintana
McGovern Medical School University and McWilliams School of Biomedical Informatics of Texas Health Science Center Houston. Emory University School of Medicine. Houston Methodist Hospital. Baylor College of Medicine. University of Rochester Medical Center.
MedComm
MedComm 2026; 7:
DOI: 10.1002/mco2.70610
Abstract
Pulmonary hypertension (PH) is a fatal condition that affects individuals with systemic sclerosis (SSc), a multiorgan fibrotic disease with limited treatment options. A central feature of PH is vascular remodeling, defined by the narrowing of the arteriole lumen due to cell proliferation and extracellular matrix deposition. Herein, we identify a central mechanism that can regulate multiple transcripts important for vascular remodeling. The highlight of our study is the demonstration that reduced pulmonary artery smooth muscle (PASMC) Nudt21, which codes for the RNA binding protein Cleavage and Polyadenylation Specificity Factor Subunit 5 (CPSF5) The, known to regulate alternative polyadenylation, results in heightened right ventricle systolic pressures in mice exposed to hypoxia-sugen. We also report that increased PASMC proliferation is present in mice with reduced PASMC Nudt21 under normoxic conditions, recapitulating features of hypoxia-sugen exposure. Our studies reveal that reduced CPSF5 leads to 3′ untranslated region shortening of PTGER3 and CBFB, the latter contributing to increased levels of proliferative transcription factor RUNX1. We also identify miR-3163 as novel negative regulator of NUDT21 expression in PH. These observations are validated in remodeled vessels from patients with SSc associated with PH and in and point to common mechanisms of RNA processing deficits that contribute to vascular remodeling in PH.
Category
Animal Models of Pulmonary Vascular Disease and Therapy
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Class III. Pulmonary Hypertension Associated with Alveolar Hypoxia
Class I. Drug-induced and Toxin-induced Pulmonary Hypertension
Class I. Pulmonary Hypertension Associated with Connective Tissue Disease
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes