title: Chaihuang-Yishen granule inhibits diabetic kidney disease in rats through blocking TGF-β/Smad3 signaling.
abstract: OBJECTIVE
  Increasing evidence shows that TGF-β1 is a key mediator in diabetic nephropathy (DN) and induces renal fibrosis positively by Smad3 but negatively by Smad7. However, treatment of DN by blocking the TGF-β/Smad pathway remains limited. The present study investigated the anti-fibrotic effect of a traditional Chinese medicine, Chaihuang-Yishen granule (CHYS), on DN.
  
  
  METHODS
  Protective role of CHYS in DN was examined in an accelerated type 1 DN induced by streptozotocin in uninephrectomized Wistar rats. CHYS, at a dose of 0.56 g/kg body weight, was administered by a daily gastric gavage for 20 weeks and the therapeutic effect and potential mechanisms of CHYS on diabetic kidney injury were examined.
  
  
  RESULTS
  Treatment with CHYS attenuated diabetic kidney injury by significantly inhibiting 24-h proteinuria and progressive renal fibrosis including glomerulosclerotic index, tubulointerstitial fibrosis index, and upregulation of extracellular matrix (collagen I, IV, and fibronectin), despite the same levels of blood glucose. Further studies revealed that inhibition of renal fibrosis in CHYS-treated diabetic rats was associated with inhibition of TGF-β1/Smad3 signaling as demonstrated by upregulation of Smad7 but downregulation of TGF-β1, TGF-β receptors, activation of Smad3, and expression of miRNA-21.
  
  
  CONCLUSIONS
  CHYS may be a therapeutic agent for DN. CHYS attenuates DN by blocking TGF-β/Smad3-mediated renal fibrosis.
authors.affiliation: Department of Pharmacology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Hao Jun
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Xiao Guang
authors.initials: XG
authors.lastname: Lu
authors.affiliation: Department of Medicine and Therapeutics, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR; and CUHK Shenzhen Research Institute, Shenzhen, China.
authors.forename: Xiao Ru
authors.initials: XR
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Wei Ku
authors.initials: WK
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Medicine and Therapeutics, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR; and CUHK Shenzhen Research Institute, Shenzhen, China.
authors.forename: Hui Yao
authors.initials: HY
authors.lastname: Lan
authors.affiliation: Department of Pharmacology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051900:Smad3 Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051906:Smad7 Protein / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D053773:Transforming Growth Factor beta1; C525740:yishen