Significance of Intraglomerular Expression of α-Smooth Muscle Actin, Desmin, and PDGF Receptor on Glomerulosclerosis in the Rat Remnant Kidney Model

To elucidate the possible pathomechanism of glomerulosclerosis by partial nephrectomy, male SD rats received 3/4 nephrectomy and were maintained without further treatment for 8 weeks (3/4 nephrectomized group). Another group received a sham operation consisting of laparotomy and manipulation of the renal pedicles but without destruction of renal tissue and were maintained without treatment for 8 weeks (sham-operated group). The following findings were observed in the 3/4 nephrectomized group. The levels of urinary protein elevated after 4 weeks and thereafter reached a plateau. A high blood pressure was present at week 8. Histopathologically, glomerulosclerotic lesions were characterized by capillary obsolescence, proliferation of glomerular cells (including mesangial cells), mesangial matrix increase, and macrophage influx, and associated with expression of α-smooth muscle actin (α-SMA) and desmin in the glomerular tuft (mainly mesangial cells) and platelet-derived growth factor (PDGF) receptor in the glomerular tuft. The present results suggest that the key pathologic changes for glomerulosclerosis are impaired endothelial cells of glomerular capillaries by rapidly increased blood flow into the remaining nephrons and the resultant production of growth factors such as PDGF leading to mesangial cell proliferation. Furthermore, the present expression of α-SMA and desmin in mesangial cells suggests a phenotype switch of mesangial cells responsible for the induction of glomerulosclerosis.