Down-regulation of aquaporin3 expression by lipopolysaccharide <i>via</i> p38/c-Jun N-terminal kinase signalling pathway in HT-29 human colon epithelial cells

Li, Fengxia; Huang, Lijia; Dong, Chuan; Wang, Junping; Wu, Hongjuan; Shuang, Shaomin

doi:10.3748/wjg.v21.i15.4547

Cited by 18 publications

(18 citation statements)

References 29 publications

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“…To our knowledge, only one study showed that changes in AQPs expression and water permeability may increase resistance to apoptosis in activated HSCs, although the metabolic impact of glycerol diffusion in activation and quiescence was not analyzed 16 . Importantly, previous studies revealed repression of AQP3 by LPS exposure in human colon epithelial HT-29 cells 17 but induction in murine 3T3-L1 adipocytes 18 , in line with AQP3 upregulation by arachidonic acid or prostaglandin in human retinal pigment epithelial cells, already suggesting a role of JNK 19 . Since in PNPLA3 I148M expressing HSCs the JNK/AP-1 pathway is strongly induced 20 , the subsequent PPARγ downregulation, led us to hypothesize that PPARγ could regulate AQPs expression in HSC in connection to the I148M variant 20 .…”

Section: Introductionsupporting

confidence: 61%

AQP3 is regulated by PPARγ and JNK in hepatic stellate cells carrying PNPLA3 I148M

Tardelli

Bruschi

Claudel

et al. 2017

Sci Rep

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Aquaglyceroporins (AQPs) allow the movement of glycerol that is required for triglyceride formation in hepatic stellate cells (HSC), as key cellular source of fibrogenesis in the liver. The genetic polymorphism I148M of the patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with hepatic steatosis and its progression to steatohepatitis (NASH), fibrosis and cancer. We aimed to explore the role of AQP3 for HSC activation and unveil its potential interactions with PNPLA3. HSC were isolated from human liver, experiments were performed in primary HSC and human HSC line LX2. AQP3 was the only aquaglyceroporin present in HSC and its expression decreased during activation. The PPARγ agonist, rosiglitazone, recovered AQP3 expression also in PNPLA3 I148M carrying HSC. When PNPLA3 was silenced, AQP3 expression increased. In liver sections from patients with NASH, the decreased amount of AQP3 was proportional to the severity of fibrosis and presence of the PNPLA3 I148M variant. In PNPLA3 I148M cells, the blockade of JNK pathway upregulated AQP3 in synergism with PPARγ. In conclusion, we demonstrated profound reduction of AQP3 in HSC carrying the PNPLA3 I148M variant in parallel to decreased PPARγ activation, which could be rescued by rosiglitazone and blockade of JNK.

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Section: Introductionsupporting

confidence: 61%

AQP3 is regulated by PPARγ and JNK in hepatic stellate cells carrying PNPLA3 I148M

Tardelli

Bruschi

Claudel

et al. 2017

Sci Rep

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“…Lipopolysaccharide, tumor necrosis factor, platelet‐activating factor, IL‐1, and other inflammatory stimuli can induce the activation of P38 in endogenous immune cells such as monocytes, endothelial cells, and neutrophils . P38 activation is closely related to apoptosis and P38 can increase the expression of c‐Myc, phosphorylation of P53 and activation of c‐Jun, to regulate apoptosis . ATF2 is a commonly recognized downstream target of P38 MAPK kinase .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of prostate cancer growth by solanine requires the suppression of cell cycle proteins and the activation of ROS/P38 signaling pathway

et al. 2016

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Solanine, a naturally steroidal glycoalkaloid in nightshade (Solanum nigrum Linn.), can inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism of solanine‐suppressing prostate cancer cell growth remains to be elucidated. This study investigates the inhibition mechanism of solanine on cancer development in vivo and in cultured human prostate cancer cell DU145 in vitro. Results show that solanine injection significantly suppresses the tumor cell growth in xenograft athymic nude mice. Solanine regulates the protein levels of cell cycle proteins, including Cyclin D1, Cyclin E1, CDK2, CDK4, CDK6, and P21 in vivo and in vitro. Also, in cultured DU145 cell, solanine significantly inhibits cell growth. Moreover, the administration of NAC, an active oxygen scavenger, markedly reduces solanine‐induced cell death. Blockade of P38 MAPK kinase cannot suppress reactive oxygen species (ROS), but can suppress solanine‐induced cell apoptosis. Also, inhibition of ROS by NAC inactivates P38 pathway. Taken together, the data suggest that inhibition of prostate cancer growth by solanine may be through blocking the expression of cell cycle proteins and inducing apoptosis via ROS and activation of P38 pathway. These findings indicate an attractive therapeutic potential of solanine for suppression of prostate cancer.

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“…Previous studies have shown that LPS, mimicking inflammation occurring during obesity, can affect the expression of several aquaglyceroporins. Indeed, LPS down-regulated AQP3 levels in human colon epithelial cells through a p38/JNK signaling pathway [37], but enhanced AQP9 expression in rat brain by an, as yet, uncharacterized signaling pathway [38]. However, it is currently unknown if LPS affects aquaglyceroporin expression in adipocytes.…”

Section: Introductionmentioning

confidence: 99%

Involvement of JNK/NFκB Signaling Pathways in the Lipopolysaccharide-Induced Modulation of Aquaglyceroporin Expression in 3T3-L1 Cells Differentiated into Adipocytes

Chiadak

Arsenijević

Grégoire

et al. 2016

IJMS

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Aquaglyceroporins, belonging to the family of aquaporins (AQPs), are integral plasma membrane proteins permeable to water and glycerol that have emerged as key players in obesity. The aim of this study was to investigate the expression profile of AQPs in undifferentiated and differentiated 3T3-L1 cells and to investigate the changes in expression of aquaglyceroporins in 3T3-L1 cells differentiated into adipocytes and subjected to lipopolysaccharide (LPS) mimicking inflammation occurring during obesity. Furthermore, the study aimed at identifying the signaling cascade involved in the regulation of aquaglyceroporins expression upon LPS stimulation. 3T3-L1 cells were grown as undifferentiated cells (UDC; preadipocytes) or cells differentiated into adipocytes (DC, adipocytes). DC were incubated in the presence or absence of LPS with or without inhibitors of various protein kinases. AQPs mRNA expression levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR). AQP1, AQP2, AQP3, AQP9 and AQP11 mRNA were expressed in both UDC and DC, whereas AQP4, AQP7 and AQP8 mRNA were expressed only in DC. In DC, LPS up-regulated AQP3 mRNA levels (p < 0.05) compared to control; these effects were inhibited by CLI095, SP600125 and BAY11-7082 (p < 0.05). LPS decreased both AQP7 and AQP11 mRNA levels (p < 0.01) in DC as compared to control; this decrease was inhibited by CLI095 and BAY11-7082 (p < 0.05) and additionally by SP00125 for AQP7 (p < 0.05). SB203580 had no effect on LPS-induced AQP3, AQP7 and AQP11 mRNA levels modulations. In conclusion, our results clearly show that many AQPs are expressed in murine 3T3-L1 adipocytes. Moreover, in DCs, LPS led to decreased AQP7 and AQP11 mRNA levels but to increased AQP3 mRNA levels, resulting from the Toll-like receptor 4 (TLR4)-induced activation of JNK and/or NFκB pathway.

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Down-regulation of aquaporin3 expression by lipopolysaccharide via p38/c-Jun N-terminal kinase signalling pathway in HT-29 human colon epithelial cells

Abstract: p38 and JNK may be promising targets for the preservation of AQP3 expression and may be beneficial to the clinical management of diarrhoea.

Cited by 18 publications

References 29 publications

AQP3 is regulated by PPARγ and JNK in hepatic stellate cells carrying PNPLA3 I148M

AQP3 is regulated by PPARγ and JNK in hepatic stellate cells carrying PNPLA3 I148M

Inhibition of prostate cancer growth by solanine requires the suppression of cell cycle proteins and the activation of ROS/P38 signaling pathway

Involvement of JNK/NFκB Signaling Pathways in the Lipopolysaccharide-Induced Modulation of Aquaglyceroporin Expression in 3T3-L1 Cells Differentiated into Adipocytes

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