The Effect of Dendritic Cells on Rat Tubulointerstitial Fibrosis and Valsartan Inhibition of Dendritic Cells

Abstract: To observe the accumulation of dendritic cells (DCs) in rat remnant kidney and its contribution to tubulointerstitial fibrosis， as well as to investigate the role of valsartan on DCs. Rat remnant kidney model was established by subtotal nephrectomy. Four groups were included， normal (n=18)， sham (n=18)， model group (SNx， n=18) and treated group with valsartan (SNxV， n=18). Groups of rats were killed at 1 week， 4 weeks， and 12 weeks， respectively. DC-SIGN⁺ DCs were observed by double immunostaining method and the images were analyzed with axioplan 2 microscopy; The expression of P-selectin， TGF-β1， α-SMA， collagen III and fibronectin were analyzed by immunohistochemistry or RT-PCR semiquantitatively， and the level of tubulointerstitial firosis (TIF) was scored. DC-SIGN⁺ DCs was gradually increased among renal tubules， interstitium and vessels， especially in interstitium， and the number of DCs in model group at 12 weeks was much more than model groups at 1 week or 4 weeks. The expression of P-selectin， TGF-β1， α-SMA， collagen III and fibronectin in tubulointerstitial areas and the degree of TIF were increased substantially in model group at 12 weeks. The accumulation of DCs in interstitium was well associated with the loss of renal function and the progression of tubulointerstitial fibrosis. Valsartan treatment inhibited the local accumulation of DCs and attenuated renal tubulointerstitial damage. The local DCs accumulation was related to tubulointerstitial fibrosis and renal dysfunction following renal ablation. Blockade to angiotensin II might be a potent way to attenuate renal immuno-inflammatory injury.

CSTR: 32200.14.cjcb.2007.05.0022