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Published on: November 10, 2021
Glomerular expression of platelet-derived growth factor (PDGF)-A, -B chain and PDGF receptor-alpha, -beta in human
Goro Uehara1, Daisuke Suzuki, Masao Toyoda
1Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, 259-1193, Japan.
Background:
Mesangial expansion is thought to be a major cause of diabetic nephropathy (DN). Platelet-derived growth factor (PDGF) plays an important role in the production of extracellular matrix proteins in renal diseases. The present study was designed to determine the expression of PDGF and PDF receptor (PDGFR) mRNA in the renal tissues of type 2 diabetic patients with DN.
Methods:
We examined open renal biopsies of 20 type 2 diabetic patients with DN, and 10 normal human kidneys (NHK). Histopathologically, the severity of DN was classified as grade I (DN I, n = 10; mild mesangial expansion) or grade II (DN II, n = 10; moderate mesangial expansion). We evaluated the expression and localization of PDGF-A, -B, and PDGFR-Alpha, -Beta using in situ hybridization, and quantified PDGF and PDGFR mRNA expression by counting all nuclei, and nuclei surrounded by PDGF-positive cytoplasm and PDGFR-positive cytoplasm, in at least ten randomly selected cross-sections of nonsclerotic glomeruli.
Results:
In all glomeruli, PDGF and PDGFR mRNAs were expressed mainly in glomerular resident cells, predominantly glomerular mesangial and epithelial cells. The percentages of cells positive for PDGF-A and PDGFR-Alpha mRNA in DN were similar to those in NHK. In contrast, the percentages of PDGF-B and PDGFR-Beta mRNA-positive cells in DN were significantly higher than those in NHK, and were significantly higher in DN I than in DN II: The percentages of cells positive for PDGF-B correlated with the PDGFR-Beta mRNA level.
Conclusions:
Our results suggest that the expression of PDGF-B and PDGFR-Beta is an important factor in histologically early glomerular lesions of DN. Mesangial expansion is thought to be a major cause of diabetic nephropathy (DN). Platelet-derived growth factor (PDGF) plays an important role in the production of extracellular matrix proteins in renal diseases. The present study was designed to determine the expression of PDGF and PDGF receptor (PDGFR) mRNA in the renal tissues of type 2 diabetic patients with DN.
Insights
Increased expression of Platelet-Derived Growth Factor-B (PDGF-B) and its receptor PDGFR-Beta is linked to early diabetic nephropathy (DN) glomerular lesions. This suggests PDGF-B/PDGFR-Beta plays a key role in the progression of DN.
Area of Science:
- Nephrology
- Diabetology
- Molecular Biology
Background:
- Diabetic nephropathy (DN) is characterized by mesangial expansion.
- Platelet-derived growth factor (PDGF) is implicated in extracellular matrix production in renal diseases.
Purpose of the Study:
- To investigate the expression of PDGF and PDGF receptor (PDGFR) mRNA in renal tissues of type 2 diabetic patients with DN.
- To correlate PDGF and PDGFR expression with the severity of DN.
Main Methods:
- Analysis of renal biopsies from 20 type 2 diabetic patients with DN (grades I and II) and 10 normal human kidneys (NHK).
- Evaluation of PDGF-A, -B, and PDGFR-Alpha, -Beta mRNA expression and localization using in situ hybridization.
- Quantification of mRNA expression by counting positive cells in nonsclerotic glomeruli.
Main Results:
- PDGF and PDGFR mRNAs were primarily expressed in glomerular mesangial and epithelial cells.
- PDGF-A and PDGFR-Alpha mRNA levels were similar in DN and NHK.
- PDGF-B and PDGFR-Beta mRNA levels were significantly higher in DN patients compared to NHK, and higher in DN grade I than grade II, with PDGF-B correlating with PDGFR-Beta.
Conclusions:
- PDGF-B and PDGFR-Beta expression is a significant factor in early-stage glomerular lesions of DN.
- These findings highlight the role of the PDGF-B/PDGFR-Beta pathway in the pathogenesis of DN.
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