title: The role of IL-7 in renal proximal tubule epithelial cells fibrosis.
abstract: BACKGROUND
  Hyperglycemia is the most important risk factor in the progression of renal fibrosis in diabetic kidney. Based on previous studies, interleukin-7 (IL-7) may exert antifibrotic activities in pulmonary fibrosis model. However, the role of IL-7 in the pathogenesis of renal tubulointerstitial fibrosis remains unclear. Thus, we hereby elucidate the effects of IL-7 in cultured renal proximal tubular epithelial cells (designated as HK-2) treated under hyperglycemic condition.
  
  
  METHODS
  Cells were cultured in high glucose (27.5mM) for 2 days. Different concentration of IL-7 (10, 50, 100 or 200ng/ml) was added in the last 24h of culture. ELISA was used to evaluate the secreted protein such as fibronectin and TGF-β(1). Western blot was used to examine the EMT marker (including α-smooth muscle actin (α-SMA) and E-cadherin), signal transducer (including Smad Smad2/3 and Smad7) and EMT initiator (e.g. Snail). Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin and Snail).
  
  
  RESULTS
  We found that IL-7 significantly attenuated high glucose-inhibited cellular growth and high glucose-induced fibrosis. More importantly, high glucose-induced up-regulation of fibronectin, TGF-β, TGF-β RII and pSmad2/3 was markedly inhibited by IL-7. On the contrary, high glucose-induced down-regulation of Smad7 was significantly reversed by IL-7 instead. IL-7 markedly inhibited high glucose-induced increase in α-SMA and Snail and decrease in E-cadherin.
  
  
  CONCLUSIONS
  We demonstrate that IL-7 has the potential to inhibit high glucose-induced renal proximal tubular fibrosis partly by modulating Smads and EMT pathway.
authors.affiliation: Graduate Institute of Biomedical Science, Chung Hwa University of Medical Technology, Tainan, Taiwan.
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Hsieh
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Liu
authors.forename: Tao-Chen
authors.initials: TC
authors.lastname: Lee
authors.forename: Jau-Shyang
authors.initials: JS
authors.lastname: Huang
authors.forename: Li-Te
authors.initials: LT
authors.lastname: Yin
authors.forename: Wen-Teng
authors.initials: WT
authors.lastname: Chang
authors.forename: Lea-Yea
authors.initials: LY
authors.lastname: Chuang
authors.forename: Jinn-Yuh
authors.initials: JY
authors.lastname: Guh
authors.forename: Min-Yuan
authors.initials: MY
authors.lastname: Hung
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Yang
mesh_terms: D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology* / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D009130:Muscle, Smooth / Q000737:chemistry; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D051785:Smad Proteins / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D005353:Fibronectins; D015851:Interleukin-7; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D005947:Glucose