DIM attenuates TGF-β1-induced myofibroblast differentiation in neonatal rat cardiac fibroblasts.

Abstract

3,3'-Diindolylmethane (DIM) is a natural component of cruciferous plants. Previous studies have shown that DIM has multiple physiological effects including anti-angiogenic, anti-inflammatory and anti-cancer effect. However, little is known about the role of DIM on myofibroblast differentiation and extracellular matrix (ECM) production. This study investigated the effect of DIM on myofibroblast differentiation and ECM production in neonatal rat cardiac fibroblasts induced by transforming growth factor β1 (TGF-β1). We found that DIM blunted TGF-β1 induced conversion of cardiac fibroblast into myofibroblast, and reduced the mRNA and protein expressions of α-smooth muscle actin (α-SMA). Furthermore, DIM also significantly decreased the mRNA expression of fibrosis markers (Collagen I, Collagen III, connective tissue growth factor (CTGF) in neonatal rat cardiac fibroblasts induced by TGF-β1. DIM attenuated the phosphorylation AKT and glycogen synthase kinase-3β (GSK-3β) induced by TGF-β1. Our results showed that DIM was a potential drug to attenuate myofibroblast differentiation and excessive ECM production induced by TGF-β1 through down-regulated AKT/GSK-3β signaling pathways.

• Authors: Jin Li, Wenbin Zhang, Rong Jiao, Zheng Yang, Yuan Yuan, Qingqing Wu, Zhefu Hu, Shizhao Xiang, Qizhu Tang
• Journal: International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 8 Issue 5 Pg. 5121-8 ( 2015) ISSN: 1936-2625 [Electronic] United States
• PMID: 26191207 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• CCN2 protein, rat
• Collagen Type I
• Collagen Type III
• Indoles
• RNA, Messenger
• Transforming Growth Factor beta1
• smooth muscle actin, rat
• Connective Tissue Growth Factor
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, rat
• Proto-Oncogene Proteins c-akt
• Glycogen Synthase Kinase 3
• 3,3'-diindolylmethane

Topics

• Actins (genetics, metabolism)
• Animals
• Animals, Newborn
• Cell Differentiation (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Collagen Type I (genetics, metabolism)
• Collagen Type III (genetics, metabolism)
• Connective Tissue Growth Factor (genetics, metabolism)
• Dose-Response Relationship, Drug
• Fibroblasts (drug effects, metabolism, pathology)
• Fibrosis
• Gene Expression Regulation
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Heart (drug effects)
• Indoles (pharmacology)
• Myofibroblasts (drug effects, metabolism, pathology)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Messenger (metabolism)
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Transforming Growth Factor beta1 (pharmacology)