STAT6 deficiency inhibits tubulointerstitial fibrosis in obstructive nephropathy.
To elucidate the contribution of signal transducer and activator of transcription (STAT) 6 to the pathophysiology of chronic renal injury, STAT6-/- mice were subjected to unilateral ureteral ligation together with wild-type control mice. STAT6-/- kidneys had more apoptotic cells and a greater influx of F4/80-positive cells than wild-type kidneys following ureteral obstruction. There was a much larger alpha-smooth muscle actin-positive area in STAT6-/- kidneys than in wild-type kidneys after ureteral ligation. However, renal fibrosis, as quantified by Masson-Trichrome staining, was not significantly exaggerated in STAT6-/- kidneys compared with wild-type kidneys. The accumulation of collagen I was significantly less in STAT6-/- kidneys than in wild-type kidneys. These observations indicate that the STAT6 signal transduction pathway exerts a protective role on renal cell apoptosis in chronic obstructive uropathy. Our findings also suggest that the STAT6 pathway may have a promotive effect on renal fibrosis by activating collagen synthesis following ureteral obstruction.
Yukawa
Kazunori
K
Department of Physiology, Wakayama Medical University, Wakayama 641-8509, Japan. kazu59@wakayama-med.ac.jp
Kishino
Masanori
M
Goda
Mikako
M
Liang
Xiang-Ming
XM
Kimura
Akihiko
A
Tanaka
Tetsuji
T
Bai
Tao
T
Owada-Makabe
Kyoko
K
Tsubota
Yuji
Y
Ueyama
Takashi
T
Ichinose
Masakazu
M
Maeda
Masanobu
M
Takeda
Kiyoshi
K
Akira
Shizuo
S
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D003094:Collagen / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology; D005355:Fibrosis; D005838:Genotype; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000378:metabolism / Q000473:pathology*; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics*; D014513:Ureter / Q000378:metabolism; D014517:Ureteral Obstruction / Q000378:metabolism / Q000473:pathology*
D000199:Actins; D004396:Coloring Agents; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D003094:Collagen