Protective effects of SOCS3 overexpression in high glucose-induced lung epithelial cell injury through the JAK2/STAT3 pathway

Duan, Weina; Xia, Zhongyuan; Liu, Min; Sun, Qian; Lei, Shaoqing; Wu, Xiaojing; Meng, Qingtao; Leng, Yan

doi:10.3892/mmr.2017.6941

Cited by 22 publications

(23 citation statements)

References 42 publications

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“…25 Duan et al demonstrated that overexpression of SOCS3 improved high glucose-induced injury of pulmonary endothelial cells through inhibition of JAK2/STAT3 signaling. 26 Another study observed that inhibition of IL-6 improved diabetic nephropathy and that the process was associated with upregulation of SOCS3. 27 Taken together, these studies indicate that SOCS3 might improve diabetes, potentially through its anti-inflammation effects.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the role of miR-221 in diabetic peripheral neuropathy and related molecular mechanisms

Wang²,

Yin³

et al. 2021

Adv Clin Exp Med

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Background. Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes, but the molecular mechanisms of DPN are still unclear.Objectives. To investigate the role of miR-221 in DPN and the related molecular mechanisms.Materials and methods. Streptozotocin (STZ) was used to establish an in vivo DPN model. An in vitro DPN model was established using high glucose-induced SH-SY5Y cells. The pain condition of rats was measured by evaluating the 50% paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Serum exosomes were extracted and identified. Expression of miR-221 in serum exosomes and serum SOCS3 expression were determined using reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Western blotting was used to measure the protein levels of SOCS3, bradykinin (BK) and prostaglandin E2 (PEG2). The dual luciferase reporter assay was performed to confirm SOCS3 3'-UTR as a target of miR-221. The serum or cell supernatant levels of PEG2, BK, interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA).Results. Induction of the lenti-miR-221 inhibitor significantly decreased the expression of miR-221 in DPN rats. Both 50% PWT and PWL values were markedly decreased in DPN rats. When miR-221 was inhibited, the 50% PWT and PWL values were both significantly increased. Knockdown of miR-221 significantly increased the expression of SOCS3 and decreased the expression of NF-κB. Furthermore, knockdown of miR-221 remarkably decreased the expression of PEG2, BK, IL-6, IL-1β, and TNF-α in both STZ-treated DPN rats and high glucose-induced SH-SY5Y cells, which was reversed by inhibition of SOCS3. The dual luciferase reporter assay showed that miR-221 directly targeted and negatively regulated SOCS3.Conclusions. Inhibition of miR-221 can reduce pain and decrease expression of inflammatory factors through targeting SOCS3 in DPN.

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Section: Discussionmentioning

confidence: 99%

Investigation of the role of miR-221 in diabetic peripheral neuropathy and related molecular mechanisms

Wang²,

Yin³

et al. 2021

Adv Clin Exp Med

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“…By up-regulating epithelial SOCS3, the inhibition of ROS production ameliorates lung inflammation induced by influenza A viruses [35]. In the models of ALI induced by high glucose and IgG immune complexes, SOCS3 overexpression is demonstrated to be a negative regulator of the JAK/STAT3 signaling pathway that reduces the inflammation of alveolar epithelial cells [36, 37]. To our knowledge, this is the first time that Gas6/Axl signaling has been associated with the SOCS3 expression of the alveolar epithelium in ALI.…”

Section: Discussionmentioning

confidence: 99%

Gas6/Axl signaling attenuates alveolar inflammation in ischemia-reperfusion-induced acute lung injury by up-regulating SOCS3-mediated pathway

Peng

Lin

et al. 2019

PLoS ONE

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Background Axl is a cell surface receptor tyrosine kinase, and activation of the Axl attenuates inflammation induced by various stimuli. Growth arrest-specific 6 (Gas6) has high affinity for Axl receptor. The role of Gas6/Axl signaling in ischemia-reperfusion-induced acute lung injury (IR-ALI) has not been explored previously. We hypothesized that Gas6/Axl signaling regulates IR-induced alveolar inflammation via a pathway mediated by suppressor of cytokine signaling 3 (SOCS3). Methods IR-ALI was induced by producing 30 min of ischemia followed by 90 min of reperfusion in situ in an isolated and perfused rat lung model. The rats were randomly allotted to a control group and IR groups, which were treated with three different doses of Gas6. Mouse alveolar epithelium MLE-12 cells were cultured in control and hypoxia-reoxygenation (HR) conditions with or without Gas6 and Axl inhibitor R428 pretreatment. Results We found that Gas6 attenuated IR-induced lung edema, the production of proinflammatory cytokines in perfusates, and the severity of ALI ex vivo. IR down-regulated SOCS3 expression and up-regulated NF-κB, and Gas6 restored this process. In the model of MLE-12 cells with HR, Gas6 suppressed the activation of TRAF6 and NF-κB by up-regulating SOCS3. Axl expression of alveolar epithelium was suppressed in IR-ALI but Gas6 restored phosphorylation of Axl. The anti-inflammatory effect of Gas6 was antagonized by R428, which highlighted that phosphorylation of Axl mediated the protective role of Gas6 in IR-ALI. Conclusions Gas6 up-regulates phosphorylation of Axl on alveolar epithelium in IR-ALI. The Gas6/Axl signaling activates the SOCS3-mediated pathway and attenuates IR-related inflammation and injury.

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“…8 Indeed, hyperglycemia may interfere with the placental profile of cytokine expression, 9 as well as with the signaling pathways modulated by those cytokines. Therefore, hyperglycemia may differently regulate SOCS3 and JAK/STAT activity, in a tissue and manner specific condition, as demonstrated in pulmonary epithelial cells, 10 macrophage, 11 vascular smooth muscle cells, 12 among others.…”

Section: Introductionmentioning

confidence: 99%

Increased expression of STAT3 and SOCS3 in placenta from hyperglycemic rats

et al. 2019

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Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated by interleukin (IL)-6 and IL-10 that generate nearly opposing responses. The suppressor of cytokine signaling 3 (SOCS3) is the negative regulator of STAT3 and plays an important role in the negative regulation of the inflammatory process. Evidence has shown the importance of STAT3 and SOCS3 during implantation and normal pregnancy. However, little is known about the relationship of both factors under hyperglycemic condition. The aim of this study was to evaluate the placenta regions exhibiting immunopositivity for STAT3 and SOCS3 in hyperglycemic rats, as well as correlate these proteins with IL-10 and IL-6 levels. It was observed increased expression of STAT3 at the labyrinth (approximately 47% of increase compared to control) and junctional zone (approximately 32% of increase compared to control) from hyperglycemic placentas. Similar results were observed to SOCS3 (approximately 71% -labyrinth- and 53% -junctional zone- of increase compared to control). The levels of IL-10 were augmented at hyperglycemic placentas (approximately 1.5 fold of increase) and they were positively correlated with the increase of STAT3 at the labyrinth and SOCS at junctional zone. Therefore, under hyperglycemic conditions, the relation between STAT3 and SOCS3 was changed, leading to unbalance of the cytokine profile.

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Protective effects of SOCS3 overexpression in high glucose-induced lung epithelial cell injury through the JAK2/STAT3 pathway

Cited by 22 publications

References 42 publications

Investigation of the role of miR-221 in diabetic peripheral neuropathy and related molecular mechanisms

Investigation of the role of miR-221 in diabetic peripheral neuropathy and related molecular mechanisms

Gas6/Axl signaling attenuates alveolar inflammation in ischemia-reperfusion-induced acute lung injury by up-regulating SOCS3-mediated pathway

Increased expression of STAT3 and SOCS3 in placenta from hyperglycemic rats

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