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Updated: Oct 2, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
PDGF receptor-alpha deficiency in glomerular mesangial cells of tenascin-C knockout mice
Kenji Matsumoto1, Noriko Hiraiwa, Atsushi Yoshiki
1Experimental Animal Division, Bio Resource Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan. kenjimat@rtc.riken.go.jp
Abstract:
Tenascin-C (TNC) knockout (TNKO) mice showed reduced proliferation of mesangial cells and abnormal restoration after habu-snake venom (HSV)-induced glomerulonephritis. In this study, we examined the relationship of TNC and platelet-derived growth factor receptor (PDGFR) in glomerular mesangial cells. TNC and PDGFR-alpha and -beta transcriptions were up-regulated in wild type (WT) mice after HSV injection, but in TNKO mice PDGFR-alpha transcription was not up-regulated. Immunohistochemistry showed that PDGFR-alpha was found in mesangial areas of colocalized alpha-smooth muscle actin, but in TNKO mice it was not detectable. In vitro studies showed that the expressions of PDGFR-alpha and -beta mRNA and protein in cultured glomerular mesangial cells (GMC) of TNKO mice were lower than those in WT GMC. These results suggest that failures of both TNC and PDGFR-alpha are a candidate for abnormal restoration of TNKO mice.
Insights
Tenascin-C (TNC) knockout mice exhibit impaired kidney repair due to reduced platelet-derived growth factor receptor (PDGFR) expression. This suggests TNC and PDGFR-alpha are crucial for mesangial cell recovery after injury.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Biology
Background:
- Tenascin-C (TNC) plays a role in kidney repair.
- Glomerulonephritis can lead to abnormal mesangial cell proliferation and restoration.
- Platelet-derived growth factor receptor (PDGFR) signaling is important in cellular processes.
Purpose of the Study:
- To investigate the relationship between Tenascin-C (TNC) and Platelet-Derived Growth Factor Receptor (PDGFR) in glomerular mesangial cells.
- To understand the molecular mechanisms behind abnormal kidney repair in TNC knockout (TNKO) mice.
Main Methods:
- Induction of glomerulonephritis using habu-snake venom (HSV) in wild-type (WT) and TNKO mice.
- Analysis of TNC, PDGFR-alpha, and PDGFR-beta gene expression via transcription and immunohistochemistry.
- In vitro studies on cultured glomerular mesangial cells (GMC) from WT and TNKO mice.
Main Results:
- HSV injection upregulated TNC, PDGFR-alpha, and PDGFR-beta in WT mice, but not PDGFR-alpha in TNKO mice.
- PDGFR-alpha, colocalized with alpha-smooth muscle actin, was detected in mesangial areas of WT mice but absent in TNKO mice.
- Cultured GMC from TNKO mice showed lower PDGFR-alpha and PDGFR-beta mRNA and protein expression compared to WT GMC.
Conclusions:
- Tenascin-C (TNC) deficiency leads to impaired upregulation of PDGFR-alpha in response to glomerulonephritis.
- Reduced expression of both TNC and PDGFR-alpha may contribute to the abnormal kidney restoration observed in TNKO mice.
- TNC and PDGFR-alpha are critical components for effective mesangial cell response and repair in glomerulonephritis.
