title: Attenuation of Tubular Injury and Renal Fibrosis by TI-HU-YIN via Reduction in Transforming Growth Factor-β1 Expression in Unilateral Ureteral Obstruction Mice.
abstract: TI-HU-YIN (JCKD), a compound composed of many Chinese herbs, is hypothesized to attenuate renal tubular injury and interstitial fibrosis. Moreover, its renoprotective effects were assessed in animal and in vitro studies. First, male C57BL/6 mice were under sham operation or unilateral ureteral obstruction (UUO) surgery, and then treated with phosphate buffer solution (PBS), aliskirin and valsartan (A+V), and JCKD for 14 days. At 7 and 14 days, mice were sacrificed and the kidney tissues were assessed for histopathological changes and transforming growth factor (TGF)-β1 expression. As compared to sham group, UUO-PBS group had more serious tubular dilatation and injury, α-smooth muscle actin-positive areas, F4/80-positive macrophages, and interstitial fibrosis. Impressively, these pathologic changes were significantly attenuated in UUO mice both treated with JCKD and A+V as compared to UUO-PBS group. At 14 days, TGF-β1 expression was significantly suppressed in kidney tissues of UUO-JCKD group as well as in UUO-A+V group. Second, TGF-β1 production was increased in macrophage J774 cells and NRK-52E proximal tubular cells stimulated by angiotensin (Ang)-II at 10 nM for 24 h and at 1 nM for 48 h, respectively. JCKD (≥ 400 μg/ml) inhibited the TGF-β1 production at baseline and stimulated by Ang II in both cell lines. Our study showed that JCKD reduced renal injury, macrophage infiltration and interstitial fibrosis possibly through suppressing the TGF-β1 expression in UUO mice. Accordingly, JCKD is potential to retard the progression of chronic kidney disease. Further studies are needed to validate its renoprotective effects in the inhibition of TGF-β1 expression and the amelioration of renal fibrosis.
authors.affiliation: Department and Institute of Physiology, and Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan, Republic of China.|Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan, Republic of China.
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Tarng
authors.affiliation: Department and Institute of Physiology, Taiwan, Republic of China.
authors.forename: I-Shan
authors.initials: IS
authors.lastname: Liu
authors.affiliation: Division of Chinese Medicine Literature and Informatics, National Research Institute of Chinese Medicine, Taipei 11221, Taiwan, Republic of China.
authors.forename: Lie-Chwen
authors.initials: LC
authors.lastname: Lin
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 11221, Taiwan, Republic of China.
authors.forename: Nien-Jung
authors.initials: NJ
authors.lastname: Chen
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D005355:Fibrosis; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012084:Renin-Angiotensin System / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000037:antagonists & inhibitors*; D014517:Ureteral Obstruction / Q000188:drug therapy*
chemical_list: D004365:Drugs, Chinese Herbal; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II