Focal tubular cell multiplication at sites on an injured nephron is a critical event in the recovery phase following acute tubular necrosis. During this process, numerous viable tubular cells exfoliate and are shed into the urine. Lysophosphatidic acid (LPA) is generated in the plasma membrane of injured cells and acts as an intercellular mediator of various biological processes, including inflammation, proliferation and repair. In the present study, exfoliated proximal tubule (PT) cells were isolated from human urine and the mitogenic effects of LPA were investigated as a model of repair and proliferation following renal injury. LPA stimulated a 23.5% increase in DNA synthesis, a 29.4% increase in cell number and an 86.6% decrease in cAMP content. All of these responses were pertussis toxin sensitive, indicating the involvement of Gi-type G-proteins in LPA signalling. Conversely, the LPA-induced DNA synthesis and the decrease in intracellular cAMP content were insensitive to wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), suggesting a mitogenic response via PI3K-independent mechanisms. Furthermore, we detected specific mRNA transcripts for the recently cloned human LPA-receptors, endothelial differentiation gene (Edg)-2 and Edg-4 (Edg-2 ≫ Edg-4) by reverse transcription-PCR in PT cells. Our data suggest that LPA may behave as a local growth factor in PT cells following tubular injury.
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November 21 2000
Mitogenic action of lysophosphatidic acid in proximal tubular epithelial cells obtained from voided human urine
Naonori KUMAGAI;
Naonori KUMAGAI
1Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
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Chiyoko N. INOUE;
1Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
Correspondence: Dr C. N. Inoue (e-mail [email protected]).
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Yoshiaki KONDO;
Yoshiaki KONDO
1Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
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Kazuie IINUMA
Kazuie IINUMA
1Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
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Publisher: Portland Press Ltd
Received:
February 14 2000
Revision Received:
June 22 2000
Accepted:
August 15 2000
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 99 (6): 561–567.
Article history
Received:
February 14 2000
Revision Received:
June 22 2000
Accepted:
August 15 2000
Citation
Naonori KUMAGAI, Chiyoko N. INOUE, Yoshiaki KONDO, Kazuie IINUMA; Mitogenic action of lysophosphatidic acid in proximal tubular epithelial cells obtained from voided human urine. Clin Sci (Lond) 1 December 2000; 99 (6): 561–567. doi: https://doi.org/10.1042/cs0990561
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