Wnt/β‐catenin signalling mediates cardiac hypertrophy in type 4 cardiorenal syndrome

Abstract

AbstractAimCardiorenal 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.MethodsIn 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.ResultsCardiac 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.ConclusionThese 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.