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 ph osphatidylinositol 4,5-bisphosphate to inhibit hydrolysis by phospholipase C gamma 1. This study investigated the expression of profilin in rat anti-T hy-1.1 mesangial proliferative glomerulonephritis (GN) and examined the eff ect of growth factors on its expression in cultured rat mesangial cells. Pr ofilin mRNA was constitutively expressed in isolated glomeruli of untreated rats. However, in glomeruli of anti-Thy-1.1 GN rats, its expression was up regulated beginning on day 1, reaching a peak level on day 4 (3.9-fold vers us control glomeruli), and decreased on day 14, as determined by competitiv e reverse transcription-PCR. Increased expression of profilin protein was c onfirmed using immunoblotting and immunohistochemistry. Immunoelectron micr oscopy revealed the presence of profilin in plasma membrane and the rough e ndoplasmic reticulum of mesangial cells, indicating that profilin was produ ced in mesangial cells. In cultured rat mesangial cells, expression of prof ilin 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 again st profilin inhibited [H-3]thymidine uptake. These findings indicated the i nvolvement 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 possib ly by affecting cell growth.