KLF15 is an essential negative regulatory factor for the cardiac remodeling response to pressure overload.

Abstract

OBJECTIVE:

To investigate the mechanism of Krüppel-like factor 15 (KLF15) in cardiac remodeling and interstitial fibrosis.

METHODS:

A rat model was established by in vivo aortic coarctation followed by a period of pressure unloading and used to measure heart function, myocardial pathological changes, and KLF15, transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF), and myocardin-related transcription factor A (MRTF-A) expression levels. In addition, cardiac fibroblasts were cultured in vitro and treated with KLF15-shRNA or KLF15 recombinant adenovirus to establish a TGF-β-mediated cardiac fibroblast hypertrophy model and analyze cell morphology, collagen secretion, and changes in the expression levels of 4 cytokines.

RESULTS:

In vivo pressure overload impaired cardiac function and resulted in myocardial hypertrophy and fibrosis. These changes were accompanied by the downregulation of KLF15 mRNA levels and increased expression of the other factors. The response to unloading was the opposite. In in vitro cell experiments, by specifically targeting the KLF15 gene, changes in the expression levels of the 4 cytokines and the amounts of collagen I and III were observed.

CONCLUSIONS:

In myocardial remodeling processes induced by mechanical or metabolic factors, KLF15 regulates TGF-β, CTGF, and MRTF-A expression and can ameliorate or even reverse myocardial fibrosis and improve cardiac function.

• Authors: Yang Yu, Jie Ma, Yingbin Xiao, Qingjun Yang, Huali Kang, Jie Zhen, Lang Yu, Lin Chen
• Journal: Cardiology (Cardiology) Vol. 130 Issue 3 Pg. 143-52 ( 2015) ISSN: 1421-9751 [Electronic] Switzerland
• PMID: 25633973 (Publication Type: Journal Article)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• CCN2 protein, rat
• Cytokines
• Klf15 protein, rat
• Kruppel-Like Transcription Factors
• RNA, Messenger
• Transcription Factors
• Transforming Growth Factor beta
• myocardin-related transcription factor-A, rat
• Connective Tissue Growth Factor
• Collagen

Topics

• Animals
• Cardiomegaly (genetics)
• Cells, Cultured
• Collagen (genetics)
• Connective Tissue Growth Factor (genetics, metabolism)
• Cytokines (metabolism)
• Disease Models, Animal
• Echocardiography
• Fibroblasts
• Fibrosis
• Heart Failure (genetics)
• Heart Function Tests
• Kruppel-Like Transcription Factors (genetics, metabolism)
• Male
• Myocardium (pathology)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Transcription Factors (genetics, metabolism)
• Transforming Growth Factor beta (genetics, metabolism)