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

Research output: Contribution to journalArticle

10 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

Fingerprint

Ureteral Obstruction
Fibrosis
Matrix Metalloproteinases
Kidney
Kidney Diseases
Nanoparticles
Collagen
Inflammation
Messenger RNA
peptide-Gly-Leu-amide

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Koike, K., Ueda, S., Yamagishi, S. I., Yasukawa, H., Kaida, Y., Yokoro, M., ... 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

Protective role of JAK/STAT signaling against renal fibrosis in mice with unilateral ureteral obstruction. / Koike, Kiyomi; Ueda, Seiji; Yamagishi, Sho ichi; Yasukawa, Hideo; Kaida, Yusuke; Yokoro, Miyuki; Fukami, Kei; Yoshimura, Akihiko; Okuda, Seiya.

In: Clinical Immunology, Vol. 150, No. 1, 01.2014, p. 78-87.

Research output: Contribution to journalArticle

Koike, K, Ueda, S, Yamagishi, SI, 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, vol. 150, no. 1, pp. 78-87. https://doi.org/10.1016/j.clim.2013.11.003
Koike, Kiyomi ; Ueda, Seiji ; Yamagishi, Sho ichi ; Yasukawa, Hideo ; Kaida, Yusuke ; Yokoro, Miyuki ; Fukami, Kei ; Yoshimura, Akihiko ; Okuda, Seiya. / Protective role of JAK/STAT signaling against renal fibrosis in mice with unilateral ureteral obstruction. In: Clinical Immunology. 2014 ; Vol. 150, No. 1. pp. 78-87.
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