title: [The effect of Janus kinase 2 inhibitor AG490 on renal tubular epithelial-myofibroblast transdifferentiation induced by interleukin-1β].
abstract: OBJECTIVE
  To investigate the effect of AG490, a Janus kinase 2 inhibitor, on epithelial-myofibroblast transdifferentiation induced by interleukin-1β (IL-1β).
  
  
  METHODS
  Cultured human renal tubular epithelial cell line (HKCs) were divided into three groups: blank control group, IL-1β (5 ng/ml) group and AG490 group (IL-1β 5 ng/ml+AG490 10 μmol/L). The cells in all groups were collected at 24, 48, 72 hours after intervention. Immunocytochemistry and Western blotting analysis were used to determine the expressions of cytokeratin-18 (CK-18) and α-smooth muscle actin (α-SMA).
  
  
  RESULTS
  The higher expression of CK-18 (1.25±0.08) and mild expression of α-SMA (0.17±0.01) were found in blank control group. In IL-1β group, the protein level of CK-18 was gradually decreased with prolongation of stimulus (24 hours : 0.69±0.04, 48 hours: 0.52±0.03, 72 hours: 0.30±0.01), while the expression level of α-SMA was gradually increased (24 hours: 0.56±0.04, 48 hours: 1.05±0.07, 72 hours: 1.43±0.07), and the difference between blank control group and IL-1β group was statistically significant (all P<0.05). The administration of AG490 could restore the expression of CK-18 (24 hours: 1.07±0.07, 48 hours: 0.93±0.06, 72 hours: 0.83±0.06), and inhibit the expression of α-SMA induced by IL-1β (24 hours: 0.33± 0.01, 48 hours: 0.52±0.01, 72 hours: 0.61±0.04). There was significant difference between AG490 group and IL-1β group (all P<0.05). The results of immunocytochemistry and that of Western blotting were identical.
  
  
  CONCLUSIONS
  IL-1β can induce the transdifferentiation of renal tubular epithelial cells, up-regulate the expression of α-SMA, induce the renal tubular epithelial cells to transform to myofibroblast, while AG490 can inhibit the effect of IL-1β.
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang 050017, Hebei, China.
authors.forename: Qing-juan
authors.initials: QJ
authors.lastname: Liu
authors.forename: Yong-hong
authors.initials: YH
authors.lastname: Shi
authors.forename: Shu-xia
authors.initials: SX
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Hao
authors.forename: Yan-ping
authors.initials: YP
authors.lastname: Cao
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Jin-ying
authors.initials: JY
authors.lastname: Wei
authors.forename: Hui-jun
authors.initials: HJ
authors.lastname: Duan
mesh_terms: D000199:Actins / Q000378:metabolism; D002460:Cell Line; D054338:Cell Transdifferentiation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D053538:Keratin-18 / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D053538:Keratin-18; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D053614:Janus Kinase 2