title: Pentraxin 3 Activates JNK Signaling and Regulates the Epithelial-To-Mesenchymal Transition in Renal Fibrosis.
abstract: OBJECTIVE
  Tubulointerstitial fibrosis can lead to end-stage renal disease. Pentraxin 3 (PTX3) is an acute phase protein produced by resident and innate immunity cells. We investigated the effect of PTX3 on cultured human proximal tubular epithelial (HK-2) cells and a rat unilateral ureteral obstruction (UUO) model of renal fibrosis.
  
  
  METHODS
  Gain-of-function experiments were used to examine the effect of recombinant human PTX3 (Rh-PTX3) on HK-2 cells. Cell proliferation (MTT assay) and in vitro cell migration were measured. The levels of PTX3, p-JNK, and EMT markers were measured using immunohistochemistry, RT-PCR, and western blotting in UUO rats and HK-2 cells.
  
  
  RESULTS
  HK-2 cells treated with Rh PTX3 did not affect cell viability, but significantly increased cell migration. Moreover, Rh-PTX3 increased the expression of snail, slug, N-cadherin, and vimentin, decreased the expression of E-cadherin, and increased the phosphorylation of JNK. SP600126 (a specific JNK inhibitor) enhanced the effects of Rh-PTX3. Rats with UUO exhibited time-dependent increased levels of PTX3, p-JNK, and vimentin, and decreased expression of E-cadherin.
  
  
  CONCLUSIONS
  Our results suggest that PTX3 induces cell migration via upregulation of EMT in a JNK-dependent mechanism, and highlight the role of PTX3 in the pathogenesis renal fibrosis.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Tung-Wei
authors.initials: TW
authors.lastname: Hung
authors.forename: Jen-Pi
authors.initials: JP
authors.lastname: Tsai
authors.forename: Shin-Huey
authors.initials: SH
authors.lastname: Lin
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Lee
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
authors.forename: Horng-Rong
authors.initials: HR
authors.lastname: Chang
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D004789:Enzyme Activation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005355:Fibrosis; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology* / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000201:enzymology / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D000683:Serum Amyloid P-Component / Q000494:pharmacology*; D014517:Ureteral Obstruction / Q000473:pathology; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D048031:JNK Mitogen-Activated Protein Kinases; D000683:Serum Amyloid P-Component; D000099153:Pentraxins