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Wnt/β‐catenin signalling mediates cardiac hypertrophy in type 4 cardiorenal syndrome
Author(s) -
Zhao Yue,
Lei Yanping,
Li Yueyan,
Zhang Jingjing,
Tang Huifang
Publication year - 2021
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/nep.13848
Subject(s) - medicine , cardiorenal syndrome , wnt signaling pathway , kidney , kidney disease , endocrinology , cardiology , signal transduction , biology , microbiology and biotechnology
Abstract Aim Cardiorenal syndrome type 4 (CRS4) is characterized by the condition that chronic kidney disease (CKD) causes sustainable injury to heart. This study focuses on exploring the mechanism underlying CRS4 and potential treatment for CRS4. Methods In the present study, Sprague Dawley (SD) rats were subjected to 5/6 subtotal nephrectomy (5/6NX) for generating animal model of CKD. Cardiac hypertrophy, kidney injury, Wnt/β‐catenin signalling and serum TNF‐α were tested at eighth week after 5/6NX. Results Cardiac hypertrophy and kidney injury were prominent and accompanied by Wnt/β‐catenin activation in rats at eighth week after 5/6NX. Blockade of Wnt/β‐catenin by ICG‐001 reduced 5/6NX‐stimulated fibronectin and podocalyxin in remnant kidney. Interestingly, ICG‐001 also inhibited hypertrophic markers β‐MHC and α‐actin and reduced cardiac hypertrophy. In addition, TNF‐α, as a systemic inflammation factor in blood circulation, was suggested to connect CKD to cardiac hypertrophy. It was demonstrated in vitro and in vivo studies that ICG‐001 is sufficient to counteract TNF‐α‐induced cardiac hypertrophy by sequestration of β‐catenin. Conclusion These results demonstrate that Wnt/β‐catenin to be a unified pathogenic pathway of heart disorder and kidney disease in CRS4. Based on that, Wnt/β‐catenin signalling could be a target of promising therapy for protecting both heart and kidney organs in CRS4.