title: Conditional Knockout of Src Homology 2 Domain-containing Protein Tyrosine Phosphatase-2 in Myeloid Cells Attenuates Renal Fibrosis after Unilateral Ureter Obstruction.
abstract: BACKGROUND
  Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) is a kind of intracellular protein tyrosine phosphatase. Studies have revealed its roles in various disease, however, whether SHP-2 involves in renal fibrosis remains unclear. The aim of this study was to explore the roles of myeloid cells SHP-2 in renal interstitial fibrosis.
  
  
  METHODS
  Myeloid cells SHP-2 gene was conditionally knocked-out (CKO) in mice using loxP-Cre system, and renal interstitial fibrosis was induced by unilateral ureter obstruction (UUO). The total collagen deposition in the renal interstitium was assessed using picrosirius red stain. F4/80 immunostaing was used to evaluate macrophage infiltration in renal tubular interstitium. Quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay were used to analyze the production of cytokines in the kidney. Transferase-mediated dUTP nick-end labeling stain was used to assess the apoptotic renal tubular epithelial cells.
  
  
  RESULTS
  Src homology 2 domain-containing protein tyrosine phosphatase-2 gene CKO in myeloid cells significantly reduced collagen deposition in the renal interstitium after UUO. Macrophage infiltration was evidently decreased in renal tubular interstitium of SHP-2 CKO mice. Meanwhile, the production of pro-inflammatory cytokines was significantly suppressed in SHP-2 CKO mice. However, no significant difference was observed in the number of apoptotic renal tubular epithelial cells between wild-type and SHP-2 CKO mice.
  
  
  CONCLUSIONS
  Our observations suggested that SHP-2 in myeloid cells plays a pivotal role in the pathogenesis of renal fibrosis, and that silencing of SHP-2 gene in myeloid cells may protect renal from inflammatory damage and prevent renal fibrosis after renal injury.
authors.forename: Jing-Fei
authors.initials: JF
authors.lastname: Teng
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.forename: Fa-Jun
authors.initials: FJ
authors.lastname: Qu
authors.forename: Qing
authors.initials: Q
authors.lastname: Yuan
authors.forename: Xin-Gang
authors.initials: XG
authors.lastname: Cui
authors.forename: Quan-Xing
authors.initials: QX
authors.lastname: Wang
authors.affiliation: Department of Urology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Dan-Feng
authors.initials: DF
authors.lastname: Xu
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis / Q000201:enzymology* / Q000473:pathology*; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000201:enzymology* / Q000473:pathology*
chemical_list: D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11