title: SOCS3 promotes inflammation and apoptosis via inhibiting JAK2/STAT3 signaling pathway in 3T3-L1 adipocyte.
abstract: The suppressor of cytokine signaling 3 (SOCS3) is an established negative feedback regulation transcription factor associated with leptin, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and growth hormone (GH). However, the regulatory mechanism of SOCS3 on inflammation and apoptosis of adipocyte is still not clear. In this study, we found an increased expression of adipocyte inflammatory cytokines TNF-α and IL-6 due to leptin treatment. Meanwhile Caspase3, a key executioner of apoptosis, was also elevated in this process. In addition, we observed that SOCS3 could promote inflammation whereas SOCS3 interference reversed this effect in LPS-induced adipocytes inflammatory model. Moreover, the expression of apoptosis-associated genes Bax, cleaved-Caspase9 and cleaved-Caspase3 were elevated along with decreased Bcl-2 expression as detected with Western blot and ELISA assay. The phosphorylation level of JAK2/STAT3 signal was inhibited by SOCS3 along with the elevated expression of IL-6, TNF-α and Caspase3. We also demonstrated that stable knockdown of SOCS3 along with SD1008, a specific inhibitor of JAK2/STAT3 signaling pathway, could significantly inhibit inflammation and apoptosis of adipocyte. Altogether, these results inferred that SOCS3 promotes adipocyte apoptosis by both aggravating inflammation and inhibiting the activity of JAK2/STAT3 signaling pathway.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Zhenjiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: sunchao2775@163.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020738:Leptin / Q000276:immunology; D051379:Mice; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D014326:Tropanes / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C524881:8-benzyl-4-oxo-8-azabicyclo(3.2.1)oct-2-ene-6,7-dicarboxylic acid; D015850:Interleukin-6; D020738:Leptin; D050796:STAT3 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; D014326:Tropanes; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D053148:Caspase 3
keywords: Adipocyte; Apoptosis; Inflammation; JAK/STAT signaling pathway; SOCS3