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Updated: Sep 12, 2026
Epithelial Cell Repopulation and Preparation of Rodent Extracellular Matrix Scaffolds for Renal Tissue Development
Published on: August 10, 2015
Infusion of platelet-derived growth factor or basic fibroblast growth factor induces selective glomerular mesangial
Abstract:
Mesangial cell (MC) proliferation and extracellular matrix expansion are involved in the pathogenesis of glomerulosclerosis and renal failure. In vitro, PDGF and basic fibroblast growth factor (bFGF) regulate MC proliferation and/or matrix production. To elucidate the role of PDGF and bFGF in vivo, equimolar concentrations of recombinant PDGF-BB or bFGF or vehicle were infused intravenously into rats over a 7-d period. Rats were either nonmanipulated ("normals") or had received a subnephritogenic dose of anti-MC antibody ("anti-Thy 1.1 rats") before the infusion period. Glomerular cell proliferation (anti-proliferating cell nuclear antigen immunostaining) on days 2, 4, and 7 was unchanged in vehicle-infused normals or anti-Thy 1.1 rats. PDGF infusion increased glomerular cell proliferation 32-fold in anti-Thy 1.1 rats and an 11-fold in normals on day 2. bFGF increased glomerular cell proliferation fourfold in anti-Thy 1.1 rats but was ineffective in normals. Induction of cell proliferation in all kidneys was limited to the glomerulus. The majority of proliferating cells were identified as MC by double immunolabeling. No significant proteinuria, glomerular leukocyte, or platelet influx developed in any group. Glomerular matrix expansion with increased deposition of type IV collagen, laminin, and fibronectin, as well as upregulated laminin and collagen IV mRNA expression was confined to PDGF-infused anti-Thy 1.1 rats. These results show that PDGF and, to a lesser degree, bFGF are selective MC mitogens in vivo and that previous subclinical injury can enhance this MC response. The data thereby support a role of these cytokines in the pathogenesis of glomerulosclerosis.
Insights
Platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) stimulate mesangial cell (MC) proliferation in vivo. Prior kidney injury amplifies MC response to PDGF, suggesting a role in glomerulosclerosis.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Medicine
Background:
- Mesangial cell (MC) proliferation and extracellular matrix expansion contribute to glomerulosclerosis and kidney failure.
- Platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) are known regulators of MCs in vitro.
Purpose of the Study:
- To investigate the in vivo roles of PDGF and bFGF in MC proliferation and glomerulosclerosis pathogenesis.
- To determine if subclinical kidney injury influences the response to these growth factors.
Main Methods:
- Recombinant PDGF-BB or bFGF was infused intravenously into rats for 7 days.
- Rats were either healthy or pretreated with anti-MC antibody (anti-Thy 1.1) to induce subclinical injury.
- Glomerular cell proliferation was assessed using anti-proliferating cell nuclear antigen (PCNA) immunostaining and MCs were identified by double immunolabeling.
Main Results:
- PDGF significantly increased glomerular MC proliferation in both normal and anti-Thy 1.1 rats, with a greater effect in the latter.
- bFGF induced MC proliferation only in anti-Thy 1.1 rats.
- PDGF infusion in anti-Thy 1.1 rats led to glomerular matrix expansion and increased deposition of collagen IV, laminin, and fibronectin.
Conclusions:
- PDGF and bFGF act as selective mesangial cell mitogens in vivo.
- Pre-existing subclinical kidney injury potentiates the MC proliferative response to PDGF.
- These findings support a role for PDGF and bFGF in the development of glomerulosclerosis.
