title: Inhibition of Jak/STAT signaling ameliorates mice experimental nephrotic syndrome.
abstract: OBJECTIVE
  This study investigated the role of JAK/STAT, an important pathway for cytokine signal transduction, in the progression of chronic glomerular diseases.
  
  
  METHODS
  BALB/c mice received a single intravenous injection of adriamycin (10 mg/kg) were sacrificed 2, 4 and 6 weeks later. In the second study, treatment with the selective JAK2 inhibitor AG490 (15 mg/kg, q.d., i.p.) or vehicle was started 5 days after adriamycin injection. Functional and pathologic markers, inflammatory infiltration, expression of pro-inflammatory cytokines and phosphorylation of JAK2/STATs were assessed.
  
  
  RESULTS
  JAK/STAT signaling was activated in adriamycin nephropathy. Phosphorylation of JAK2, STAT1 and STAT3 was significantly inhibited by AG490 (p <0.01). Compared to the vehicle-treated controls, AG490 treatment did not reduce proteinuria 2 weeks after induction of the disease, but resulted in significant decrease in proteinuria and serum creatinine at week 6 (p <0.05). Glomerulosclerosis, tubulointerstitial lesions and renal alpha-SMA expression were also significantly suppressed by AG490 treatment at week 6 (p < 0.01). In addition, AG490 inhibited the expression of MCP-1 mRNA, accompanied by reduced interstitial infiltration of macrophages and T cells (p <0.05).
  
  
  CONCLUSIONS
  This study suggests that activation of JAK/STAT signaling is involved in the progression of glomerular diseases with proteinuric state.
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Niansheng
authors.initials: N
authors.lastname: Yang
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Yuefang
authors.initials: Y
authors.lastname: Huang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Mingqian
authors.initials: M
authors.lastname: Luo
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Liang
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009404:Nephrotic Syndrome / Q000473:pathology / Q000503:physiopathology*; D010766:Phosphorylation; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D020032:Tyrphostins / Q000494:pharmacology*