Abstract
Cardiac fibrosis is an important pathogenic feature of the remodeling process that occurs in heart failure and myocardial infarction. This process is triggered by a number of signaling pathways that result in excessive production and deposition of extracellular matrix (ECM). Connective Tissue Growth factor (CTGF, CCN2), a member of CCN (Cyr61, Ctgf, Nov) family, is a multifunctional protein that is expressed in both cardiac myocytes and fibroblasts that is a key regulator of the fibrotic response. CTGF is a critical downstream target of transforming growth factor-β (TGF-β) signaling in the cardiovascular system. Kruppel-like factor 15 (KLF15) is a transcription factor that is expressed in both cardiomyocytes and cardiac fibroblasts and serves as a negative regulator of pathologic remodeling. Our group has demonstrated that KLF15 inhibits cardiac hypertrophy in response to pressure overload. Recently, we have shown that KLF15 is a novel negative regulator of CTGF expression in the heart via its ability to counteract Smad signaling at the CTGF promoter. From a clinical standpoint, progress has been made in utilizing CTGF levels as a biomarker for fibrotic diseases. In this chapter, we will summarize studies of CTGF in heart disease and discuss its importance in cardiac remodeling. In addition, potential therapeutic strategies targeting CTGF will be discussed.
Keywords
- Idiopathic Pulmonary Fibrosis
- Brain Natriuretic Peptide
- Cardiac Remodel
- Pressure Overload
- Cardiac Fibroblast
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Acknowledgement
Our research is supported by NIH grants HL72952, HL75427, HL76754, HL086548, HL084154 and P01 HL48743 (to M.K.J.); and HL 086614 (to S.H.); and Dominic Visconsi Scholarship Award (to S.H.); and American Heart Association Postdoctoral Fellowship 0725297B (to D.K.); and a Kanae Foundation for the Promotion of Medical Science grant (to D.K.).
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Kawanami, D., Haldar, S.M., Jain, M.K. (2010). Role of Connective Tissue Growth Factor in Cardiac Fibrosis. In: Perbal, A., Takigawa, M., Perbal, B. (eds) CCN Proteins in Health and Disease. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3779-4_10
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