Kielin/chordin‐like protein deficiency aggravates pressure overload‐induced cardiac dysfunction and remodeling via P53/P21/CCNB1 signaling in mice

• DOI: 10.1096/fj.202301841r
• Publication Date: 2024-02-29T14:55:15Z
• Authors: Yao Xu; Zihui Zheng; Heng Pan; Mengmeng Zhao; Jishou Zhang; Shanshan Peng; Jianfang Liu; Wei Pan; Zheng Yin; Shuwan Xu; Cheng Wei; Juan‐Juan Qin; Yingzhong Lin; Jun Wan; Menglong Wang
• Keywords: Pressure overload; Cardiac Fibrosis; Ventricular remodeling

Abstract Targeting cardiac remodeling is regarded as a key therapeutic strategy for heart failure. Kielin/chordin‐like protein (KCP) secretory with 18 cysteine‐rich domains and associated kidney liver fibrosis. However, the relationship between KCP remains unclear. Here, we aimed to investigate role of in induced by pressure overload explore its potential mechanisms. Left ventricular (LV) expression was measured real‐time quantitative PCR , western blotting, immunofluorescence staining overload‐induced mice. Cardiac function were evaluated wide‐type (WT) mice knockout (KO) echocardiography, which further confirmed histological analysis hematoxylin eosin Masson staining. RNA sequence performed LV tissue from WT KO identify differentially expressed genes related signaling pathways. Primary fibroblasts (CFs) used validate regulatory mechanisms during down‐regulated progression overload, mainly fibroblasts. deficiency significantly aggravated dysfunction remodeling. revealed that cell division, cycle, P53 pathway, while cyclin B1 (CCNB1) most up‐regulated gene. Further investigation vivo vitro suggested promoted proliferation CFs via P53/P21/CCNB1 pathway. Taken together, these results aggravates