Effects of the isothiocyanate sulforaphane on TGF‐β1‐induced rat cardiac fibroblast activation and extracellular matrix interactions
| Autor: | Wayne Carver, Charity Fix, Mohamad Azhar, Amanda Carver‐Molina, Mrinmay Chakrabarti |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Integrins Physiology Cellular differentiation Clinical Biochemistry Article Rats Sprague-Dawley Transforming Growth Factor beta1 Extracellular matrix 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Isothiocyanates Fibrosis medicine Animals Fibroblast Extracellular Matrix Proteins Superoxide Dismutase Chemistry Myocardium Hydrogels Cell Biology Fibroblasts medicine.disease Matrix Metalloproteinases Extracellular Matrix Cell biology 030104 developmental biology medicine.anatomical_structure Sulfoxides 030220 oncology & carcinogenesis Cattle Collagen Signal transduction Myofibroblast Heme Oxygenase-1 Signal Transduction Sulforaphane Transforming growth factor |
| Zdroj: | J Cell Physiol |
| ISSN: | 1097-4652 0021-9541 |
| Popis: | An important step in many pathological conditions, particularly tissue and organ fibrosis, is the conversion of relatively quiescent cells into active myofibroblasts. These are highly specialized cells that participate in normal wound healing but also contribute to pathogenesis. These cells possess characteristics of smooth muscle cells and fibroblasts, have enhanced synthetic activity secreting abundant extracellular matrix components, cytokines, and growth factors, and are capable of generating contractile force. As such, these cells have become potential therapeutic targets in a number of disease settings. Transforming growth factor β (TGF-β) is a potent stimulus of fibrosis and myofibroblast formation and likewise is an important therapeutic target in several disease conditions. The plant-derived isothiocyanate sulforaphane has been shown to have protective effects in several pathological models including diabetic cardiomyopathy, carcinogenesis, and fibrosis. These studies suggest that sulforaphane may be an attractive preventive agent against disease progression, particularly in conditions involving alterations of the extracellular matrix and activation of myofibroblasts. However, few studies have evaluated the effects of sulforaphane on cardiac fibroblast activation and their interactions with the extracellular matrix. The present studies were carried out to determine the potential effects of sulforaphane on the conversion of quiescent cardiac fibroblasts to an activated myofibroblast phenotype and associated alterations in signaling, expression of extracellular matrix receptors, and cellular physiology following stimulation with TGF-β1. These studies demonstrate that sulforaphane attenuates TGF-β1-induced myofibroblast formation and contractile activity. Sulforaphane also reduces expression of collagen-binding integrins and inhibits canonical and noncanonical TGF-β signaling pathways. |
| Databáze: | OpenAIRE |
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