TGF-beta and Fas Expression in Human Proximal Tubular Cell (HPTC) in the Presence of Proteinuria

Seo, Ji A; Jo, Sang Kyung; Han, Kum Hyun; Sung, Su Ah; Lee, Ji Eun; Lee, So Young; Kim, Sang Wook; Cha, Dae Ryong; Cho, Won Yong; Kim, Hyung Kyu

Abstract

BACKGROUND: Glomerular diseases of diverse origins are characterized by heavy proteinuria and tubulointerstitial changes in pathology. Numerous studies have recently demonstrated that interstitial fibrosis and tubular atrophy are better predictors of renal disease progression compared with glomerular pathology. One of the important mechanisms of these tubulointerstitial injury is tubulointerstitial damage due to increased protein trafficking across the proximal tubular epithelial cells. We tested the hypothesis that tubular cells exposed to high concentration of protein express TGF-beta, which can be related to tubulointerstitial fibrosis, and Fas antigen, which can be associated with tubular cell apoptosis.
METHODS
Cultured human proximal tubular cells were incubated with varying concentrations of BSA (1, 10 mg/mL) and nephrotic range proteinuria, due to diabetic nephropathy (1, 10 mg/mL), with or without inactivation of complement. After 24 hr-incubation period, the expressions of TGF-beta and Fas mRNA were examined by RT-PCR.
RESULTS
The amount of expression of TGF-beta was increased in BSA 10 mg/mL group (0.78+/-0.12, p=0.016) and in diabetic proteinuria 10 mg/mL group (0.7+/-0.08, p=0.012) compared to control group which was incubated in medium alone (0.48+/-0.02), and the amount of expression of Fas was increased in BSA 10 mg/mL group (0.97+/-0.09, p=0.021) and showed increased tendency in diabetic proteinuria 10 mg/mL group (0.94+/-0.14, p=0.067) also. Furthermore, the anti TGF-beta antibody ameliorated the increased albumin-induced expression of Fas.
CONCLUSION
Collectively, our results showed that protein overload increased the expression of TGF-beta & Fas, which can play an important role in tubulointerstitial atrophy by inducing apoptosis of renal tubular cells.