Cardiac fibroblasts are predisposed to convert into myocyte phenotype: specific effect of transforming growth factor beta
| Autor: | Brijesh Bhambi, Ronald J. Tomek, Mahboubeh Eghbali, Cheryl Woods |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
DNA Replication
Male medicine.medical_treatment Molecular Sequence Data Fluorescent Antibody Technique Myosins Microfilament Extracellular matrix Transforming Growth Factor beta medicine Animals Myocyte Fibroblast Cells Cultured Multidisciplinary Base Sequence biology Muscles Myocardium Growth factor Cell Differentiation Transforming growth factor beta Fibroblasts Molecular biology Actins Fibronectin Actin Cytoskeleton medicine.anatomical_structure biology.protein RNA Rabbits DNA Probes Oligonucleotide Probes Research Article Thymidine Transforming growth factor |
| Zdroj: | Proceedings of the National Academy of Sciences. 88:795-799 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.88.3.795 |
| Popis: | Cardiac fibroblasts are mainly responsible for the synthesis of major extracellular matrix proteins in the heart, including fibrillar collagen types I and III and fibronectin. In this report we show that these cells, when stimulated by transforming growth factor beta 1 (TGF-beta 1), acquire certain myocyte-specific properties. Cultured cardiac fibroblasts from adult rabbit heart were treated with TGF-beta 1 (10-15 ng/ml) for different periods of time. Northern hybridization analysis of total RNA showed that cells treated with TGF-beta 1 for 24 hr expressed mRNA corresponding to sarcomeric actin mRNA. Immunofluorescence staining and light microscopy showed that cultured cardiac fibroblasts treated with TGF-beta 1 became stained with a monoclonal antibody to muscle-specific actin. After treatment of quiescent cells with TGF-beta 1, cell proliferation (as measured by [3H]thymidine incorporation) was moderately increased (1.5-fold, P less than 0.001). NIH 3T3 cells and human skin fibroblasts, treated with TGF-beta 1, did not express sarcomeric actin mRNA. Treatment of cardiac fibroblasts with the mitogenic agent phorbol 12-myristate 13-acetate or with norepinephrine, angiotensin II, or interleukin 1 beta did not induce myocyte-specific actin mRNA. Cultured cardiac fibroblasts at the subconfluent stage, when exposed to TGF-beta 1 in the presence of 10% fetal bovine serum, gave rise to a second generation of slowly growing cells that expressed muscle-specific actin filaments. Our findings demonstrate that cardiac fibroblasts can be made to differentiate into cells that display many characteristics of cardiac myocytes. TGF-beta 1 seems to be a specific inducer of such conversion. |
| Databáze: | OpenAIRE |
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