Related Experiment Videos
TGF-beta and CTGF have overlapping and distinct fibrogenic effects on human renal cells
Elizabeth Gore-Hyer1, Daniel Shegogue, Malgorzata Markiewicz
1Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston 29425, USA.
Abstract:
Transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) are ubiquitously expressed in various forms of tissue fibrosis, including fibrotic diseases of the kidney. To clarify the common and divergent roles of these growth factors in the cells responsible for pathological extracellular matrix (ECM) deposition in renal fibrosis, the effects of TGF-beta and CTGF on ECM expression in primary human mesangial (HMCs) and human proximal tubule epithelial cells (HTECs) were studied. Both TGF-beta and CTGF significantly induced collagen protein expression with similar potency in HMCs. Additionally, alpha(2)(I)-collagen promoter activity and mRNA levels were similarly induced by TGF-beta and CTGF in HMCs. However, only TGF-beta stimulated collagenous protein synthesis in HTECs. HTEC expression of tenascin-C (TN-C) was increased by TGF-beta and CTGF, although TGF-beta was the more potent inducer. Thus both growth factors elicit similar profibrogenic effects on ECM production in HMCs, while promoting divergent effects in HTECs. CTGF induction of TN-C, a marker of epithelial-mesenchymal transdifferentiation (EMT), with no significant induction of collagenous protein synthesis in HTECs, may suggest a more predominant role for CTGF in EMT rather than induction of excessive collagen deposition by HTECs during renal fibrosis.
Insights
Transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) have similar roles in kidney fibrosis cells (HMCs) but different effects in kidney epithelial cells (HTECs). CTGF may drive epithelial-mesenchymal transdifferentiation more than collagen deposition.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Biology
Background:
- Transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) are implicated in renal fibrosis.
- Understanding their distinct cellular roles in extracellular matrix (ECM) deposition is crucial for fibrotic disease research.
Purpose of the Study:
- To investigate the common and divergent effects of TGF-beta and CTGF on ECM production in human mesangial cells (HMCs) and human proximal tubule epithelial cells (HTECs).
- To elucidate the specific roles of these growth factors in the cellular mechanisms underlying renal fibrosis.
Main Methods:
- Primary human mesangial cells (HMCs) and human proximal tubule epithelial cells (HTECs) were treated with TGF-beta and CTGF.
- Collagen protein expression, alpha(2)(I)-collagen promoter activity, mRNA levels, and tenascin-C (TN-C) expression were analyzed.
Main Results:
- Both TGF-beta and CTGF potently induced collagen protein and mRNA expression in HMCs.
- Only TGF-beta significantly stimulated collagenous protein synthesis in HTECs.
- Both growth factors increased tenascin-C (TN-C) in HTECs, with TGF-beta being more potent.
Conclusions:
- TGF-beta and CTGF exhibit similar profibrotic effects on ECM production in HMCs.
- These growth factors display divergent roles in HTECs, with CTGF potentially playing a greater role in epithelial-mesenchymal transdifferentiation (EMT) than collagen deposition.