›› 2018, Vol. 38 ›› Issue (3): 265-.doi: 10.3969/j.issn.1674-8115.2018.03.005

• Original article (Basic research) • Previous Articles     Next Articles

Effect of GP130 small molecular inhibitor SC144 on renal interstitial fibrosis in mice with unilateral ureteral obstruction

GONG Ying-liang*, DONG Yu*, LI Yu-feng, ZHU Ya-ju, JIN Jing, WEI Min-jiang   

  1. Department of Pedi-Nephrology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
  • Online:2018-03-28 Published:2018-05-03
  • Supported by:
    Research Fund of Shanghai Municipal Commission  of Health and Family Planning, 201640193, 20144Y0267; Clinical Medicine Grand Support of Xinhua Hospital, 15LC02)

Abstract: Objective · To investigate the effect of glycoprotein 130 (GP130) inhibitor SC144 on extracellular matrix accumulation and JAK2/STAT3
signaling pathway in unilateral ureteral obstruction (UUO) mouse model, and explore its mechanism. Methods · Eighteen female BALB/c mice were
randomly divided into 3 groups i.e. sham group, UUO group and SC144 group. All mice were sacrificed at day 14 and kidneys were harvested for
further analysis. The changes of renal tissue morphology and pathology were observed by H-E and Masson staining. The expression of α-smooth muscle
actin (α-SMA) and infiltration of macrophage cells were assayed by immunohistochemical staining. The levels of collagen-I, collagen-IV, monocyte
chemoattractant protein-1 (MCP-1), transforming growth factor-β (TGF-β) mRNA were analyzed by real-time PCR. The activation of JAK2 and STAT3
was measured by Western blotting. Results · There was a trend toward decreased renal tubular lesion and renal interstitial fibrosis in SC144 group (H-E,
P=0.052; Masson, P=0.063). SC144 significantly inhibited the levels of α-SMA, type I/type IV collagen and TGF-β mRNA (all P<0.05). Compared with
UUO group, the phosphorylation levels of JAK2 and STAT3 were significantly decreased in SC144 group (both P<0.05). Conclusion · The treatment
of UUO mouse model with SC144 can inhibit the activation of α-SMA, attenuate the phosphorylation of STAT3, reduce extracellular matrix protein
deposition following injury and renal tubular epithelial-mesenchymal transition (EMT) via JAK2/STAT3 signaling pathway, indicating its potential in
attenuating interstitial fibrosis in obstructive nephropathy.

Key words: glycoprotein 130 (GP130), renal interstitial fibrosis, unilateral ureteral obstruction (UUO), signal transduction and activator of transcription 3 (STAT3), epithelial-mesenchymal transition (EMT)