title: Protective role of JAK/STAT signaling against renal fibrosis in mice with unilateral ureteral obstruction.
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.
authors: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. Electronic address: koike_kiyomi@kurume-u.ac.jp.
authors: Kiyomi
authors: K
authors: Koike
authors: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors: Seiji
authors: S
authors: Ueda
authors: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors: Sho-ichi
authors: S
authors: Yamagishi
authors: Division of Cardio Vascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors: Hideo
authors: H
authors: Yasukawa
authors: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors: Yusuke
authors: Y
authors: Kaida
authors: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors: Miyuki
authors: M
authors: Yokoro
authors: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors: Kei
authors: K
authors: Fukami
authors: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
authors: Akihiko
authors: A
authors: Yoshimura
authors: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors: Seiya
authors: S
authors: Okuda
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D005260:Female; D005355:Fibrosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000166:cytology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011725:Pyridines / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000473:pathology
chemical_list: D016207:Cytokines; D011725:Pyridines; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D053612:Janus Kinases; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse
keywords: JAK; MMP-2; Renal fibrosis; SOCS; STAT; UUO