Expression of profilin, an actin-binding protein, in rat experimental glomerulonephritis and its upregulation by basic fibroblast growth factor in cultured rat mesangial cells.
Profilin binds to actin monomer to regulate actin polymerization, and to phosphatidylinositol 4,5-bisphosphate to inhibit hydrolysis by phospholipase Cgamma1. 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-beta. 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.
Tamura
Masahito
M
Second Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.|Department of Biochemistry, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Tanaka
Hiroshi
H
Second Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Yashiro
Akira
A
Second Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Osajima
Akihiko
A
Second Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Okazaki
Masahiro
M
Second Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Kudo
Hideaki
H
Department of Anatomy, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Doi
Yoshiaki
Y
Department of Anatomy, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Fujimoto
Sunao
S
Department of Anatomy, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Higashi
Ken
K
Department of Biochemistry, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Nakashima
Yasuhide
Y
Second Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Hirano
Hideyasu
H
Department of Biochemistry, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
D000199:Actins / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003285:Contractile Proteins; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000378:metabolism* / Q000473:pathology; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism*; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051304:Profilins; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D018800:Thy-1 Antigens / Q000276:immunology; D015854:Up-Regulation
D000199:Actins; D000911:Antibodies, Monoclonal; D003285:Contractile Proteins; D016326:Extracellular Matrix Proteins; D008840:Microfilament Proteins; D016376:Oligonucleotides, Antisense; C495740:Pfn1 protein, rat; D051304:Profilins; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D016222:Fibroblast Growth Factor 2