title: Role of keratinocyte growth factor in the pathogenesis of autosomal dominant polycystic kidney disease.
abstract: BACKGROUND
  Previous studies have shown that the expression and distribution of keratinocyte growth factor (KGF), also known as FGF-7 (fibroblast growth factor-7) or HBGF-7 (heparin-binding growth factor-7), may be implicated in kidney cyst formation and expansion. However, there are no data on KGF expression in human autosomal dominant polycystic kidney disease (ADPKD) tissue, and it is unknown whether it affects ADPKD cyst-lining epithelial cell epithelial cell proliferation.
  
  
  METHODS
  The expression and distribution of KGF and KGF receptor (KGFR) mRNA in ADPKD cystic and normal kidney tissues were examined using quantitative real-time polymerase chain reaction (PCR) and in situ hybridization. KGF and KGFR protein expression in the above tissues was analysed by immunohistochemistry and western blot. The effect of KGF on cyst-lining epithelial cell proliferation was assessed by MTT assay, and its effect on the cyst-lining epithelial cell cycle was analysed by flow cytometry. The effect of KGF on cyclin D1 and P21(wafl) gene expression in cyst-lining epithelial cells was also determined.
  
  
  RESULTS
  KGF and KGFR mRNA expression in ADPKD cysts was higher than in normal kidney tissues. KGF and KGFR protein expression was also higher in ADPKD cysts and was localized to cyst-lining epithelial cells, tubular and interstitial cells. In vitro experiments revealed that KGF promoted cyst-lining epithelial cell proliferation, and decreased the ratio of G0/G1 phase but increased that of S phase. In response to KGF, the expression of the cyclin D1 gene in cyst-lining epithelial cells increased markedly while P21(wafl) expression decreased.
  
  
  CONCLUSIONS
  KGF and KGFR expression was upregulated in ADPKD kidney tissues. KGF stimulated the proliferation of cyst-lining epithelial cell in vitro by regulating the expression of cyclin D1 and P21(wafl) genes. KGF may play a role in pathogenesis of ADPKD.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People's Republic of China. chlmei1954@126.com
authors.forename: Changlin
authors.initials: C
authors.lastname: Mei
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Mao
authors.forename: Xuefei
authors.initials: X
authors.lastname: Shen
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Dai
authors.forename: Bing
authors.initials: B
authors.lastname: Tang
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wu
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: Shuzhong
authors.initials: S
authors.lastname: Zhang
authors.forename: Haidan
authors.initials: H
authors.lastname: Zhao
authors.forename: Tianmei
authors.initials: T
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000096:biosynthesis / Q000235:genetics*; D005434:Flow Cytometry; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000096:biosynthesis / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D012333:RNA, Messenger; D051523:Fibroblast Growth Factor 7; D019938:Cyclin D1; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor