TGF-beta and Fas Expression in Human Proximal Tubular Cell (HPTC) in the Presence of Proteinuria.
- Author:
Ji A SEO
1
;
Sang Kyung JO
;
Kum Hyun HAN
;
Su Ah SUNG
;
Ji Eun LEE
;
So Young LEE
;
Sang Wook KIM
;
Dae Ryong CHA
;
Won Yong CHO
;
Hyung Kyu KIM
Author Information
1. Department of Internal Medicine, College of Medicine, Korea University, Korea. wonyong@korea.ac.kr
- Publication Type:Original Article
- Keywords:
Proteinuria;
Human proximal tubular cell;
TGF-beta;
Fas
- MeSH:
Antigens, CD95;
Apoptosis;
Atrophy;
Complement System Proteins;
Diabetic Nephropathies;
Disease Progression;
Epithelial Cells;
Fibrosis;
Humans*;
Pathology;
Protein Transport;
Proteinuria*;
RNA, Messenger;
Transforming Growth Factor beta*
- From:Korean Journal of Nephrology
2002;21(6):896-904
- CountryRepublic of Korea
- Language:Korean
-
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.
