Urotensin II Induces Cardiac Fibrosis through the TGF-β/Smad Signaling Pathway during the Development of Cardiac Hypertrophy

Abstract

Myocardial fibrosis is an important pathological phenomenon of cardiac remodeling that is induced by hypertension, myocardial ischemia, valvular heart disease, hypertrophic cardiomyopathy, and other heart diseases and can progress to heart failure. Urotensin II (UII) is regarded as a cardiovascular autacoid/hormone that is not only the most potent vasoconstrictor in mammals but also involved in cardiac remodeling. However, the molecular mechanisms responsible for UII-induced cardiac fibrosis have not yet been fully elucidated. Therefore, we aimed to investigate the effect of UII on myocardial fibrosis in cardiac hypertrophy and the mechanism of UII-induced cardiac fibrosis. Cardiac tissue from mice subjected to Transverse aortic constriction (TAC) was collected. Cardiac hypertrophy, myocardial fibrosis, and the expression of UII protein were assessed using echocardiography and pathological and molecular biological analyses. The effect of UII on fibrosis was evaluated in UII-treated mice and isolated rat primary cardiac fibroblasts, and the results indicated that UII induced significant myocardial fibrosis and increases in the proliferation and fibrotic responses both in mice and cultured fibroblasts. Mechanistically, UII treatment induced activation of the TGF-β/Smad signaling pathway, which was suppressed by the UII receptor antagonist. In conclusion, UII plays critical roles in cardiac fibrosis by modulating the TGF-β/Smads signaling pathway, which may be a promising therapeutic target in hypertrophic cardiomyopathy and related problems, such as cardiac remodeling and heart failure.

Study on the mechanism underlying Trichosanthis peel injection‐induced improvements in myocardial fibrosis markers in patients with chronic heart failure

“…Thus, it is concluded that TGFβ/Smad plays an important role in improving cardiac function and heart failure. 14 The essence of ventricular remodelling of heart failure is to mark the deficiency of the actual condition, and the treatment needs to distinguish the primary and secondary characteristics of the condition. In the early stage, heart failure is mainly manifested as the deficiency of heart and pulmonary functions, which gradually affects the spleen and kidney.…”

“…Meanwhile, inhibition of the TGF‐β/Smad signalling pathway can alleviate myocardial fibrosis and CHF. Thus, it is concluded that TGF‐β/Smad plays an important role in improving cardiac function and heart failure 14 . The essence of ventricular remodelling of heart failure is to mark the deficiency of the actual condition, and the treatment needs to distinguish the primary and secondary characteristics of the condition.…”

Associations of Transcription Factor 21 Gene Polymorphisms with the Growth and Body Composition Traits in Broilers

“…In silico analysis suggested that the g.-1243C>T was located in the regions of potential binding of BACH1 [20], and the g.-911T>G was located in multiple transcription factor binding regions (GATA4, SMAD1, and SOX17). Studies have shown that these transcription factors all play important roles in animal heart development [21][22][23][24][25]. It is hypothesized that the TCF21 gene g.-911T>G regulates the HW trait probably through binding to transcription factors (GATA4, SMAD1, and SOX17) to influence the activity of regulatory elements in this region.…”

“…Myocardial ischemia [20] g.-1171T>C --g.-911T>G T GATA4 Key regulators of heart gene expression [21,22] SMAD1 protects cardiomyocytes from ischemia-reperfusion injury [23] SOX17 Early heart development in mouse embryos [24,25] g.-891C>T ---…”

Transcriptomic and ChIP-seq Integrative Analysis Identifies KDM5A-Target Genes in Cardiac Fibroblasts

“…Regarding the pathways involving these DEGs, the KEGG analysis indicated enrichment in focal adhesion, ECM-receptor interaction, cell adhesion, arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, and dilated cardiomyopathy. These signaling pathways have been proven to be widely related to cardiac fibrosis (24)(25)(26)(27)(28). However, the links among these pathways have not yet been analyzed.…”