title: [Effects of rosiglitazone on the expression connective tissue growth factor in tubulointerstitium in KKA(y) mice].
abstract: OBJECTIVE
  To observe the expression of connective tissue growth factor (CTGF) in the tubulointerstitium in type 2 diabetic KKA(y) mice and the effect of rosiglitazone on it.
  
  
  METHODS
  KKA(y) and C57 BL/6 mice aged 16 weeks ( n = 5 in each group) were sacrificed as controls before treatment. Another 20 KKA(y) mice were treated with rosiglitazone (30 mg x kg (-1) d (-1), n = 10) or placebo (n = 10). The mice were sacrificed at 20 and 24-week-age (n = 5 at each time point). Protein expression of transforming growth factor-beta1 (TGF-beta1 ), CTGF, peroxisome proliferator-activated receptor-gamma (PPARgamma) , and fibronectin were assayed by Western blot, while protein CTGF, PPARgamma, and alpha-smooth muscle actin ( alpha-SMA) were assayed by immunohistochemistry in kidney tissue sections.
  
  
  RESULTS
  Proteinuria was significantly decreased in mice aged 24 weeks treated by rosiglitazone than same-aged mice treated with placebo [ (44. 53+/-1. 96) vs (63. 66 +/-5. 57) microg/24 h, P < 0. 05 ]. The expressions of TGF-beta1, CTGF, and fibronectin in mice aged 20 weeks treated with rosiglitazone decreased by 37% , 21% , and 52% than same-aged control (P <0. 01) , and those were decreased by 61% , 50% , and 51% in mice aged 24 weeks treated with rosiglitazone compared with same-aged control mice (P < 0. 01). CTGF in the tubulointerstitium were respectively downregulated by 25% and 44. 9% in treated mice aged 20 weeks and 24 weeks compared with the same-aged control mice ( P < 0. 01). The PPARgamma appeared in diabetic mice and increased by 18. 1% in mice aged 24 weeks and treated with rosiglitazone than the same-aged control mice (P <0. 05).
  
  
  CONCLUSIONS
  Heterogeneous rosiglitazone may upregulate the expression of PPARgamma in renal cortex, and remarkably inhibit the expressions of CTGF in the tubulointerstitium and renal cortex in diabetic KKA(y) mice.
authors.affiliation: Department of Nephrology, PUMC Hospital, CAMS and PUMC, Beijing 100730, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qin
authors.forename: Xue-wang
authors.initials: XW
authors.lastname: Li
authors.forename: Yu-bing
authors.initials: YB
authors.lastname: Wen
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Li-meng
authors.initials: LM
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Duan
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D055513:Connective Tissue Growth Factor; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005353:Fibronectins / Q000096:biosynthesis; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D007672:Kidney Cortex / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D047495:PPAR gamma / Q000819:agonists / Q000096:biosynthesis; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: C526318:CCN2 protein, mouse; D005353:Fibronectins; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; D053773:Transforming Growth Factor beta1; D000077154:Rosiglitazone; D055513:Connective Tissue Growth Factor