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Mesangioproliferati...
Mesangioproliferative Kidney Diseases and Platelet-Derived Growth Factor-Mediated AXL Phosphorylation
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Bian, Q. (author)
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Anderson, J. C. (author)
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Zhang, X. W. (author)
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Huang, Z. Q. (author)
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- Ebefors, Kerstin, 1977 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Nyström, Jenny, 1972 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine
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Hall, S. (author)
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Novak, L. (author)
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Julian, B. A. (author)
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Willey, C. D. (author)
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Novak, J. (author)
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English.
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In: Kidney Medicine. - : Elsevier BV. - 2590-0595. ; 3:6
- Related links:
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http://www.kidneymed...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- Rationale & Objective: Immunoglobulin A nephropathy (IgAN) is a common glomerular disease, with mesangial cell proliferation as a major feature. There is no disease-specific treatment. Platelet-derived growth factor (PDGF) contributes to the pathogenesis of IgAN. To better understand its pathogenic mechanisms, we assessed PDGF-mediated AXL phosphorylation in human mesangial cells and kidney tissue biopsy specimens. Study Design: Immunostaining using human kidney biopsy specimens and in vitro studies using primary human mesangial cells. Setting & Participants: Phosphorylation of AXL was assessed in cultured mesangial cells and 10 kidney-biopsy specimens from 5 patients with IgAN, 3 with minimal change disease, 1 with membranous nephropathy, and 1 with mesangioproliferative glomerulonephritis (GN). Predictor: Glomerular staining for phospho-AXL in kidney biopsy specimens of patients with mesangioproliferative diseases. Outcomes: Phosphorylated AXL detected in biopsy tissues of patients with IgAN and mesangioproliferative GN and in cultured mesangial cells stimulated with PDGF. Analytic Approach: t test, Mann-Whitney test, and analysis of variance were used to assess the significance of mesangial cell proliferative changes. Results: Immunohistochemical staining revealed enhanced phosphorylation of glomerular AXL in IgAN and mesangioproliferative GN, but not in minimal change disease and membranous nephropathy. Confocal-microscopy immunofluorescence analysis indicated that mesangial cells rather than endothelial cells or podocytes expressed phospho-AXL. Kinomic profiling of primary mesangial cells treated with PDGF revealed activation of several protein-tyrosine kinases, including AXL. Immunoprecipitation experiments indicated association of AXL and PDGF receptor proteins. An AXL-specific inhibitor (bemcentinib) partially blocked PDGF-induced cellular proliferation and reduced phosphorylation of AXL and PDGF receptor and the downstream signals (AKT1 and ERK1/2). Limitations: Small number of kidney biopsy specimens to correlate the activation of AXL with disease severity. Conclusions: PDGF-mediated signaling in mesangial cells involves transactivation of AXL. Finding appropriate inhibitors to block PDGF-mediated transactivation of AXL may provide new therapeutic options for mesangioproliferative kidney diseases such as IgAN.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
Keyword
- receptor tyrosine kinase
- signaling networks
- pdgf
- beta
- progression
- expression
- contribute
- glomeruli
- cells
- state
- Urology & Nephrology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Bian, Q.
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Anderson, J. C.
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Zhang, X. W.
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Huang, Z. Q.
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Ebefors, Kerstin ...
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Nyström, Jenny, ...
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show more...
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Hall, S.
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Novak, L.
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Julian, B. A.
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Willey, C. D.
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Novak, J.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Urology and Neph ...
- Articles in the publication
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Kidney Medicine
- By the university
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University of Gothenburg