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J Am Soc Nephrol 11:423-433, 2000
© 2000 American Society of Nephrology

Expression of Profilin, an Actin-Binding Protein, in Rat Experimental Glomerulonephritis and Its Upregulation by Basic Fibroblast Growth Factor in Cultured Rat Mesangial Cells

MASAHITO TAMURA*,{dagger}, HIROSHI TANAKA*, AKIRA YASHIRO*, AKIHIKO OSAJIMA*, MASAHIRO OKAZAKI*, HIDEAKI KUDO{ddagger}, YOSHIAKI DOI{ddagger}, SUNAO FUJIMOTO{ddagger}, KEN HIGASHI{dagger}, YASUHIDE NAKASHIMA* and HIDEYASU HIRANO{dagger}

* Second Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
{dagger} Department of Biochemistry, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
{ddagger} Department of Anatomy, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.

Correspondence to Dr. Hiroshi Tanaka, Second Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu 807-8555, Japan. Phone: +81 93 603 1611; Fax: +81 93 691 6913; E-mail: h-tanaka{at}med.uoeh-u.ac.jp

Abstract. Profilin binds to actin monomer to regulate actin polymerization, and to phosphatidylinositol 4,5-biphosphate to inhibit hydrolysis by phospholipase C{gamma}1. This study investigated the expression of profilin in rat anti-Thy-1.1 mesangial proliferative glomerulonephritis (GN) and examined the effect of growth factors on its expression in cultured rat mesangial cells. Profilin mRNA was constitutively expressed in isolated glomeruli of untreated rats. However, in glomeruli of anti-Thy-1.1 GN rats, its expression was upregulated beginning on day 1, reaching a peak level on day 4 (3.9-fold versus control glomeruli), and decreased on day 14, as determined by competitive reverse transcription-PCR. Increased expression of profilin protein was confirmed using immunoblotting and immunohistochemistry. Immunoelectron microscopy revealed the presence of profilin in plasma membrane and the rough endoplasmic reticulum of mesangial cells, indicating that profilin was produced in mesangial cells. In cultured rat mesangial cells, expression of profilin mRNA and protein was upregulated by basic fibroblast growth factor but not by platelet-derived growth factor or transforming growth factor-ß. Suppression of profilin expression using an antisense oligonucleotide against profilin inhibited [3H]thymidine uptake. These findings indicated the involvement of profilin in anti-Thy-1.1 GN and suggest that the upregulation of profilin might be involved in the progression of anti-Thy-1.1 GN possibly by affecting cell growth.




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