This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by ARON, D. C. Articles by ABBOUD, H. E. Search for Related Content PubMed PubMed Citation Articles by ARON, D. C. Articles by ABBOUD, H. E.

Synthesis and Binding of Insulin-Like Growth Factor I by Human Glomerular Mesangial Cells^*

DAVID C. ARON, JAMES L. ROSENZWEIG and HANNA E. ABBOUD

Divisions of Endocrinology and Nephrology, Department of Medicine, Veterans Administration Medical Center, Case Western Reserve University Cleveland, Ohio 44106

Address all correspondence and requests for reprints to: David C. Aron, M.D., Division of Endocrinology, Veterans Administration, Medical Center 151W, 10701 East Boulevard, Cleveland, Ohio 44106.

Insulin-like growth factor I (IGF-I) has been found in the kidney, but its precise cellular localization is not known. Since there is evidence that IGF-I is an autocrine factor i n many tissues and since murine mesangial cells have IGF-I receptors, we examined whether human mesangial cells produce IGF-I. Culture medium conditioned by mesangial cells was concentrated by reverse phase chromatography and applied to a Sephadex G-100 column equilibrated in a denaturing buffer. Two major species with apparent mol wt (MW) of 7,500 and 25,000 daltons were identified by IGF-I RIA. To determine whether the high MW species possessed IGF-I binding activity, appropriate fractions were desalted, incubated with [¹²⁵I]Thr⁵⁹-IGF-I for 2 h at 30 C, and applied to a Sephadex G-100 column equilibrated in a nondissociating buffer. The major peak of radioactivity was confined to a high MW region; there was no radioactivity in the fractions corresponding to 7,500 daltons. Further characterization of 7,500 dalton IGF-I immunoreactive species by reverse phase high performance liquid chromatography showed that it coeluted with synthetic human IGF-I. Isoelectric focusing revealed it to have a pi between 8.1 and 8.5, corresponding to the pi of human IGF-I of 8.25. Northern blot analyses of poly(A)⁺ RNA from human mesangial cells and human liver using a cDNA probe for human IGF-I showed that a 2.0-kilobase transcript predominated in the mesangial cells, whereas the liver contained 1.1- and 2.0-kilobase species. Specific binding of IGF-I to mesangial cells was demonstrated, and competition curves indicated a rank order of potency (IGF-I > IGF-II > insulin) consistent with type I IGF receptors. We conclude that human mesangial cells 1) express IGF-I mRNA transcripts, 2) secrete IGF-I and IGF-I-binding activity, and 3) possess specific IGF-I receptors. These data suggest that IGF-I may act as an autocrine or paracrine factor that regulates glomerular cell functions.

^* This work was supported by the V.A. Medical Research Service, NIH Grant DK-33665, and a Grant-in-Aid from the American Heart Association.

Current address: Joslin Diabetes Center, 1 Joslin Place, Boston, Massachusetts 02215.

Established Investigator of the American Heart Association.

Received August 5, 1988.

This article has been cited by other articles:

				B. Haraldsson, J. Nystrom, and W. M. Deen Properties of the Glomerular Barrier and Mechanisms of Proteinuria Physiol Rev, April 1, 2008; 88(2): 451 - 487. [Abstract] [Full Text] [PDF]

				P. Ruggenenti, C. Flores, C. Aros, B. Ene-Iordache, R. Trevisan, C. Ottomano, and G. Remuzzi Renal and Metabolic Effects of Insulin Lispro in Type 2 Diabetic Subjects With Overt Nephropathy Diabetes Care, February 1, 2003; 26(2): 502 - 509. [Abstract] [Full Text] [PDF]

				I. Tack, S. J. Elliot, M. Potier, A. Rivera, G. E. Striker, and L. J. Striker Autocrine Activation of the IGF-I Signaling Pathway in Mesangial Cells Isolated From Diabetic NOD Mice Diabetes, January 1, 2002; 51(1): 182 - 188. [Abstract] [Full Text] [PDF]

				D. E. Varlam, M. M. Siddiq, L. A. Parton, and H. Rüssmann Apoptosis Contributes to Amphotericin B- Induced Nephrotoxicity Antimicrob. Agents Chemother., March 1, 2001; 45(3): 679 - 685. [Abstract] [Full Text]

				J. L. Haylor, I. H. Mckillop, S. D. Oldroyd, and M. A. El Nahas IGF-I inhibitors reduce compensatory hyperfiltration in the isolated rat kidney following unilateral nephrectomy Nephrol. Dial. Transplant., January 1, 2000; 15(1): 87 - 92. [Abstract] [Full Text] [PDF]

				Z. Guan, S. Y. Buckman, L. D. Baier, and A. R. Morrison IGF-I and insulin amplify IL-1beta -induced nitric oxide and prostaglandin biosynthesis Am J Physiol Renal Physiol, April 1, 1998; 274(4): F673 - F679. [Abstract] [Full Text] [PDF]

				C. K. Abrass, A. K. Berfield, and D. L. Andress Heparin binding domain of insulin-like growth factor binding protein-5 stimulates mesangial cell migration Am J Physiol Renal Physiol, December 1, 1997; 273(6): F899 - F906. [Abstract] [Full Text] [PDF]

				A. K. Berfield, D. Spicer, and C. K. Abrass Insulin-like Growth Factor I (IGF-I) Induces Unique Effects in the Cytoskeleton of Cultured Rat Glomerular Mesangial Cells J. Histochem. Cytochem., April 1, 1997; 45(4): 583 - 594. [Abstract] [Full Text] [PDF]