Safflower extract: a novel renal fibrosis antagonist that functions by suppressing autocrine TGF-beta
| Autor: | Tao-Chen Lee, Min-Yuan Hung, Ching-Jen Wang, Yi-Shiuan Liu, Hsiang-Chun Teng, Jau-Shyang Huang, Jeng-Hsien Yeh, Chien-Ya Hung, Tung-Nan Liao, Lea-Yea Chuang, Yu-Lin Yang, Tai-An Chiang, Fang Rong Chang, Tsung-Jen Hung, Jinn-Yuh Guh, Wen-Teng Chang, Shan-Yu Chang |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Administration Oral SMAD Nephron Biology Kidney Biochemistry Models Biological Rats Sprague-Dawley Transforming Growth Factor beta1 Fibrosis Transforming Growth Factor beta Internal medicine TGF beta signaling pathway Renal fibrosis medicine Animals Medicine Chinese Traditional Autocrine signalling Fibroblast Molecular Biology Dose-Response Relationship Drug Growth factor Cell Biology medicine.disease Fibronectins Rats medicine.anatomical_structure Endocrinology Intercellular Signaling Peptides and Proteins Signal Transduction |
| Zdroj: | Journal of cellular biochemistry. 104(3) |
| ISSN: | 1097-4644 |
| Popis: | Progressive renal disease is characterized by the accumulation of extracellular matrix proteins in the renal interstitium. Hence, developing agents that antagonize fibrogenic signals is a critical issue facing researchers. The present study investigated the blood-circulation-promoting Chinese herb, safflower, on fibrosis status in NRK-49F cells, a normal rat kidney interstitial fibroblast, to evaluate the underlying signal transduction mechanism of transforming growth factor-beta (TGF-beta), a potent fibrogenic growth factor. Safflower was characterized and extracted using water. Renal fibrosis model was established both in vitro with fibroblast cells treated with beta-hydroxybutyrate and in vivo using rats undergone unilateral ureteral obstruction (UUO). Western blotting was used to examine protein expression in TGF-beta-related signal proteins such as type I and type II TGF-beta receptor, Smads2/3, pSmad2/3, Smads4, and Smads7. ELISA was used to analyze bioactive TGF-beta1 and fibronectin levels in the culture media. Safflower extract (SE) significantly inhibited beta-HB-induced fibrosis in NRK cells concomitantly with dose-dependent inhibition of the type I TGF-beta1 receptor and its down-stream signals (i.e., Smad). Moreover, SE dose-dependently enhanced inhibitory Smad7. Thus, SE can suppress renal cellular fibrosis by inhibiting the TGF-beta autocrine loop. Moreover, remarkably lower levels of tissue collagen were noted in the nephron and serum TGF-beta1 of UUO rats receiving oral SE (0.15 g/3 ml/0.25 kg/day) compared with the untreated controls. Hence, SE is a potential inhibitor of renal fibrosis. We suggest that safflower is a novel renal fibrosis antagonist that functions by down-regulating TGF-beta signals. |
| Databáze: | OpenAIRE |
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