The presence of protein in the urine of patients with renal disease is an adverse prognostic feature. It has therefore been suggested that proteinuria per se may be responsible for the development of renal tubulo-interstitial scarring and fibrosis, and disturbances in tubular cell growth and proliferation. We have used the opossum kidney proximal tubular cell line to investigate the effects of albumin on cell growth. The effect of albumin on cell proliferation was investigated by cell counting and measurement of [3H]thymidine incorporation. We studied the effect of recombinant human albumin on the activity of p44/p42 extracellular-signal-regulated mitogen-activated protein kinase (MAP kinase) using an in vitro kinase assay, and immunoblotting with antibodies against active extracellular-signal-regulated kinase (ERK). The effects of the ERK inhibitor PD98059 were also examined. Recombinant human albumin was found to stimulate proliferation of opossum kidney cells in a dose-dependent manner, with maximal stimulation at a concentration of 1 mg/ml. In addition, recombinant human albumin activated ERK in a time-dependent (maximal after 5 min) and dose-dependent (maximal at 1 mg/ml) fashion. These effects on cell proliferation and ERK activity were inhibited by PD98059, and were not reproduced by ovalbumin or mannitol. The data therefore indicate that albumin is able to stimulate growth and proliferation of proximal tubular cells that is dependent on the ERK family of MAP kinases. The potential importance of this pathway in the development of renal disease is discussed.
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February 09 2000
Albumin stimulates p44/p42 extracellular-signal-regulated mitogen-activated protein kinase in opossum kidney proximal tubular cells
Richard DIXON;
Richard DIXON
*Department of Cell Physiology and Pharmacology, Leicester University School of Medicine, P.O. Box 138, Maurice Shock Medical Sciences Building, University Road, Leicester LE1 9HN, U.K.
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Nigel J. BRUNSKILL
*Department of Cell Physiology and Pharmacology, Leicester University School of Medicine, P.O. Box 138, Maurice Shock Medical Sciences Building, University Road, Leicester LE1 9HN, U.K.
†Department of Nephrology, Leicester University School of Medicine, P.O. Box 138, Maurice Shock Medical Sciences Building, University Road, Leicester LE1 9HN, U.K.
Correspondence: Dr Nigel J. Brunskill, at the Department of Cell Physiology and Pharmacology, University of Leicester (e-mailn[email protected]).
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Publisher: Portland Press Ltd
Received:
June 28 1999
Revision Received:
October 05 1999
Accepted:
November 16 1999
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 98 (3): 295–301.
Article history
Received:
June 28 1999
Revision Received:
October 05 1999
Accepted:
November 16 1999
Citation
Richard DIXON, Nigel J. BRUNSKILL; Albumin stimulates p44/p42 extracellular-signal-regulated mitogen-activated protein kinase in opossum kidney proximal tubular cells. Clin Sci (Lond) 1 March 2000; 98 (3): 295–301. doi: https://doi.org/10.1042/cs0980295
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