title: Kruppel-like factor 15 modulates renal interstitial fibrosis by ERK/MAPK and JNK/MAPK pathways regulation.
abstract: OBJECTIVE
  Renal interstitial fibrosis is a hallmark of progressive chronic kidney disease (CKD). Previous studies reported that kruppel-like factor 15 (KLF15) is an important regulator of cardiac fibrosis and could reduce the expression of extracellular matrix in mesangial cells. However, the role of this transcription factor in renal interstitial fibrosis has not been reported.
  
  
  METHODS
  In this study, we examined KLF15 expression in the remnant kidney of 5/6 nephrectomized rats 12 or 24 weeks after operation. In vitro we examined the effect of altered KLF15 expression on the production of extracellular matrix and the pro-fibrotic factor CTGF in rat renal fibroblasts (NRK-49F), and further explored the related mechanisms.
  
  
  RESULTS
  The level of KLF15 was drastically decreased in the renal interstitium of 5/6 nephrectomized rats with progressive interstitial fibrosis, especially at 24 weeks. Our in vitro evidence showed that overexpression of KLF15 repressed basal and transforming growth factor-β1 (TGF-β1)-induced extracellular matrix and CTGF in NRK-49F cells. In addition, TGF-β1-mediated activation of extracellular-regulated kinase (ERK) / mitogen-activated protein kinase (MAPK) and Jun N-terminal kinase (JNK) /MAPK downregulated KLF15 expression and increased the level of extracellular matrix and CTGF, and all these effects were completely abolished by ERK1/2 inhibitor and JNK inhibitor in NRK-49F cells.
  
  
  CONCLUSIONS
  Our findings implicate that KLF15 plays an important role and may prove to be an antifibrotic factor in renal interstitial fibrosis through regulation of ERK/MAPK and JNK/MAPK signaling pathways.
authors.affiliation: Kidney Institute of PLA, Department of Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Guiqun
authors.initials: G
authors.lastname: Wu
authors.forename: Xiangchen
authors.initials: X
authors.lastname: Gu
authors.forename: Lili
authors.initials: L
authors.lastname: Fu
authors.forename: Changlin
authors.initials: C
authors.lastname: Mei
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005355:Fibrosis; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D007674:Kidney Diseases / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C520013:Klf15 protein, rat; D051741:Kruppel-Like Transcription Factors; D048031:JNK Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases