Therapeutic effects of suppressors of cytokine signaling in diabetic nephropathy.
Inflammation is an important pathophysiological mechanism in diabetic nephropathy (DN). Tubular epithelial cell-myofibroblast transdifferentiation (TEMT), which can be induced by many cytokines, is an important event in DN. Oncostatin M (OSM), an inflammatory cytokine, can induce TEMT in vitro. The suppressors of cytokine signaling (SOCS) proteins are negative-feedback regulators of cytokine signaling. The purpose of this study was to investigate the role of SOCS in DN. The results demonstrated that overexpression of SOCS ameliorated proteinuria, the expression of α-SMA and OSM in tubular epithelial cells, and interstitial extracellular matrix accumulation in the renal tissue of CD-1 mice. In addition, our previous studies indicated that OSM induced TEMT by activating the JAK/STAT pathway, which could be inhibited by SOCS. These results indicate that overexpression of SOCS has a therapeutic effect in DN.
Department of Pathology (QL, FY, SL, JH, WL, HD), Hebei Medical University, Shijiazhuang, China.
Qingjuan
Q
Liu
Lingling
L
Xing
Lei
L
Wang
Fang
F
Yao
Shuxia
S
Liu
Jun
J
Hao
Wei
W
Liu
Huijun
H
Duan
D000199:Actins / Q000378:metabolism*; D000818:Animals; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D015316:Genetic Therapy; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D053683:Oncostatin M / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; C544013:alpha-smooth muscle actin, mouse; D053683:Oncostatin M
SOCS; diabetic nephropathy; epithelial-myofibroblast transdifferentiation; oncostatin M