Citations 1
CDCP1 Deletion Protects Against Pressure Overload-Induced Cardiac Dysfunction and Fibrosis in Mice
Pereira, Naveen, Ghazal, Rachad, wang, Min, Cao, Jenny Jia Ling, Wang, Li , Sherman, William , John, August, Vyas, Hridyanshu , Roos, Carolyn, Huang, Runqing, Ördög, Tamás , Trussoni, Christy, Lim, Do Young , Sinagra, Gianfranco, Weinshilboum, Richard M. , Liu, Duan , Lambert, Laura , Miller, Jordan , Tschumperlin, Daniel, Srinivas, Akshatha N. , Sherman, Will A , Ordog, Tamas , Wang, Chen , Baker, Darren J , Weinshilboum, Richard M. , Liu, Duan , Lambert, Laura J, Pereira, Naveen, Ghazal, Rachad , Cao, Jenny Jia Ling , Wang, Li, Marín-Goñi, Irene , Wang, Chen , Trussoni, Christy E. , Baker, Darren J. , Sinagra, Gianfranco , Tschumperlin, Daniel J.
No container title available | May 8, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Human genomic studies link reduced CUB domain-containing protein 1 (CDCP1) expression with myocardial recovery in heart failure. While CDCP1 regulates cardiac fibroblast proliferation in vitro, it’s in vivo role in cardiac fibrosis remains unclear. Using a Cdcp1 -knockout (KO) angiotensin II/phenylephrine mouse model, we show that Cdcp1 deletion reduces echocardiographic left ventricular mass, histologic cardiac fibrosis, and pro-fibrotic gene expression, along with decreased fibroblast activation and inflammatory markers. Spatial transcriptomics identified a pressure overload–expanded fibroblast subpopulation enriched for growth factor and TGF-β signaling (FB5), which was markedly attenuated in Cdcp1 -KO hearts, alongside reduction of a pro-inflammatory cardiomyocyte subtype (CM4). Complementary studies in human ventricular fibroblasts demonstrate that CDCP1 knockdown reduced extracellular matrix gene expression and collagen I deposition. These findings establish CDCP1 as a regulator of cardiac fibrotic remodeling in vivo and open avenues for its further investigation as a potential therapeutic target.