The last decade has witnessed a phenomenal increase in our understanding of the biological role of lysophosphatidic acid (LPA) and has led to an appreciation of this critical serum-derived growth factor released from platelets. We herein summarize recent observations that collectively support the hypothesis that LPA may play a key role in the pathogenesis of initiation and progression of proliferative glomerulonephritis. LPA synergistically stimulates mesangial cell proliferation in combination with platelet-derived growth factor in primary culture. The mechanism of co-mitogenesis is likely to be mediated by the prolonged activation of mitogen-activated protein kinase which is stimulated by platelet-derived growth factor and LPA through different mechanisms. LPA contracts cultured mesangial cells and has properties in common with other pressor molecules including mobilization of intracellular Ca2+ and promotion of Ca2+ entry through dihydropyridine-sensitive calcium channels. LPA receptor mRNA has been identified in isolated glomeruli dissected from renal biopsy samples of patients with IgA nephropathy. All of these facts have led us to postulate that LPA is produced within glomeruli and that LPA's mitogenic as well as haemodynamic action contribute to the pathological process of mesangial proliferative glomerulonephritis. The possible production of LPA as an autocrine factor from mesangial cells themselves has also been discussed.
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April 01 1999
Lysophosphatidic acid and mesangial cells: implications for renal diseases
Chiyoko N. INOUE;
1Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai 980-8574, Japan
Correspondence: Dr C. N. Inoue.
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Murray EPSTEIN;
Murray EPSTEIN
*The Nephrology Section, VA Medical Center and The University of Miami School of Medicine, 1201 N.W. 16th Street, Miami, FL 33125, U.S.A., and
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Hayley G. FORSTER;
Hayley G. FORSTER
*The Nephrology Section, VA Medical Center and The University of Miami School of Medicine, 1201 N.W. 16th Street, Miami, FL 33125, U.S.A., and
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Osamu HOTTA;
Osamu HOTTA
†Department of Nephrology, Sendai Shakaihoken Hospital, 3-16-1 Tsutsumi-machi, Sendai 981-8501, Japan
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Yoshiaki KONDO;
Yoshiaki KONDO
1Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai 980-8574, Japan
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Kazuie IINUMA
Kazuie IINUMA
1Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai 980-8574, Japan
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Publisher: Portland Press Ltd
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 1999
1999
Clin Sci (Lond) (1999) 96 (4): 431–436.
Citation
Chiyoko N. INOUE, Murray EPSTEIN, Hayley G. FORSTER, Osamu HOTTA, Yoshiaki KONDO, Kazuie IINUMA; Lysophosphatidic acid and mesangial cells: implications for renal diseases. Clin Sci (Lond) 1 April 1999; 96 (4): 431–436. doi: https://doi.org/10.1042/cs0960431
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