Citations 2
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.
Novel association of NAV3 with dilated cardiomyopathy and its role in cardiac fibrosis
wang, Min, Ghazal, Rachad , Srinivas, Akshatha N. , Nguyen, Thanh Thanh L. , Murthy, Vishakantha , McNamara, D., Skime, Michelle , Batzler, Anthony , Jenkins, Gregory D. , Barlera, Simona, Mestroni, Luisa, Merlo, Marco, Pinet, Florence, Krejčí, Jan, Chaloupka, Anna , Groote, Pascal. De, Weinshilboum, RM, Tschumperlin, Daniel J. , Liu, Duan , Pereira, Naveen, McNamara, Dennis M. , Nguyen, Thanh Thanh L. , Wang, Min , Ghazal, Rachad , Wang, Min , McNamara, Dennis M , Skime, Michelle K , Pileggi, Silvana , Mestroni, Luisa , Pinet, Florence , Krejčí, Jan , Chaloupka, Anna , de Groote, Pascal , Weinshilboum, Richard M. , Tschumperlin, Daniel J , Liu, Duan , Pereira, Naveen L , Pileggi, Silvana , Mestroni, Luisa , Merlo, Marco , Pinet, F , Krejčí, Jan , Groote, Pascal de
American Journal of Physiology-Heart and Circulatory Physiology | January 29, 2026 | Volume: 330 | Issue: 3 | Pages: H686-H696
This study uncovers a previously unrecognized role for NAV3 in TGF-β1-driven cardiac fibroblast activation. We show that NAV3 facilitates profibrotic remodeling through noncanonical signaling and cell cycle arrest, independently of SMAD2/3. These findings position NAV3 as a novel regulator of fibroblast phenotype and a potential modulator of cardiac fibrosis.