Protective role of JAK/STAT signaling against renal fibrosis in mice with unilateral ureteral obstruction

Kiyomi Koike, Seiji Ueda, Sho ichi Yamagishi, Hideo Yasukawa, Yusuke Kaida, Miyuki Yokoro, Kei Fukami, Akihiko Yoshimura, Seiya Okuda

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18 Citations (Scopus)

Abstract

Inflammation is involved in renal fibrosis, a final common pathway for kidney diseases. To clarify how JAK/STAT/SOCS system was involved in renal fibrosis, UUO was induced in BALB/c or SOCS3+/- mice in the presence or absence of JAK inhibitor-incorporated nanoparticle (pyridine6-PGLA). UUO increased pSTAT3 and subsequently elevated SOCS3 levels in the obstructed kidneys. pSTAT3 levels were further increased in SOCS3+/- mice. UUO-induced renal fibrosis was markedly suppressed in SOCS3+/- mice, while it was aggravated by pre-treatment with pyridine6-PGLA. Although there were no differences in renal mRNA levels of TGF-β and collagens between wild and SOCS3+/- mice, MMP-2 activity was enhanced in SOCS3+/- UUO mice. Activated MMP-2 was completely suppressed by pyridine6-PGLA-pre-treatment. TNF-α one of JAK/STAT activators, increased pSTAT3 levels and subsequently induced MMP-2 activation in proximal tubular cells. These results suggest that JAK/STAT3 signaling may play a role in repair process of renal fibrosis in UUO partly via MMP-2 activation.

Original languageEnglish
Pages (from-to)78-87
Number of pages10
JournalClinical Immunology
Volume150
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

Keywords

  • JAK
  • MMP-2
  • Renal fibrosis
  • SOCS
  • STAT
  • UUO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Koike, K., Ueda, S., Yamagishi, S. I., Yasukawa, H., Kaida, Y., Yokoro, M., Fukami, K., Yoshimura, A., & Okuda, S. (2014). Protective role of JAK/STAT signaling against renal fibrosis in mice with unilateral ureteral obstruction. Clinical Immunology, 150(1), 78-87. https://doi.org/10.1016/j.clim.2013.11.003