RGS2 is a negative regulator of STAT3-mediated Nox1 expression

Lee, Hyung-Kyoung; Park, Dae-Weon; Bae, Jun Ho; Kim, Hyung Jun; Shin, Dong-Gu; Park, Jong Seon; Lee, Jingu; Lee, Sung Joong; Bae, Yoe‐Sik; Baek, Suk‐Hwan

doi:10.1016/j.cellsig.2011.11.015

Cited by 23 publications

(23 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Foam cell formation is a common step of early lesions in atherosclerosis development and the acute atherosis process of preeclamptic pregnancy. 21 Interestingly, Lee et al 17 showed that toll-like receptor 4 stimulation decreased RGS2 mRNA expression and induced foam cell formation in macrophages. 33 In a subsequent study, the same group showed that RGS2 reduced toll-like receptor 2-mediated NADPH oxidase 1 (Nox1) transcription by negatively regulating STAT3.…”

Section: Discussionmentioning

confidence: 99%

“…Toll-like receptormediated expression of Nox1 is important for the generation of reactive oxygen species by macrophages. 17 This in turn is necessary for macrophage transformation to foam cells during the innate immune response. 17 Thus, macrophage activation could potentially represent the mechanism associating acute atherosis and atherosclerotic disease in the women with the rs4606 G allele.…”

Section: Discussionmentioning

confidence: 99%

“…17,18 The subtype RGS2 negatively regulates G protein signaling initiated by vasoconstrictor ligands, such as Ang II, 18 and several observations point to a role for RGS2 in the control of blood pressure. 18,19 Recently, the 3′UTR C1114G polymorphism in RGS2 (rs4606), has been associated with hypertension and reduced RGS2 expression.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Single Nucleotide Polymorphisms in G Protein Signaling Pathway Genes in Preeclampsia

et al. 2013

View full text Add to dashboard Cite

Preeclampsia is a pregnancy specific disorder and a risk factor for later cardiovascular disease. The cause and detailed pathophysiology remains unknown. G protein signaling is involved in a variety of physiological processes, including blood pressure regulation. We assessed whether distributions of 3 single nucleotide polymorphisms in genes coding for components of G protein signaling pathways that have been associated with hypertension differ between women with preeclampsia and normotensive pregnant women; the G protein β3 subunit gene ( GNB3 ) C825T polymorphism (rs5443), the angiotensin II type 1 receptor gene ( AGTR1 ) 3′UTR A1166C polymorphism (rs5186), and the regulator of G protein signaling 2 gene ( RGS2 ) 3′UTR C1114G polymorphism (rs4606). Two separate Norwegian study populations were used; a large population based study and a smaller, but clinically well-described pregnancy biobank. A descriptive study of 43 women with eclampsia was additionally included. In the population-based study, an increased odds of preeclampsia (odds ratio, 1.21; [95% confidence interval, 1.05–1.40]; P =0.009) and recurrent preeclampsia (odds ratio, 1.43; [95% confidence interval, 1.06–1.92];, P =0.017) was found in women carrying the rs4606 CG or GG genotype. In early-onset preeclamptic patients with decidual spiral artery biopsies available (n=24), the rs4606 CG or GG genotype was more frequent in those with acute atherosis (resembling early stage of atherosclerosis) compared with those without: odds ratio, 15.0; (95% confidence interval, 2.02–111.2); P =0.004. No association was found between preeclampsia and the rs5443 or the rs5186. The genotype distribution in eclamptic women was not different from preeclamptic women. In conclusion, RGS2 rs4606 may affect the risk and progression of preeclampsia.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Single Nucleotide Polymorphisms in G Protein Signaling Pathway Genes in Preeclampsia

et al. 2013

View full text Add to dashboard Cite

show abstract

“…[16][17][18] ROS generation has also been found to be important for LPS signaling in macrophages, and LPS-induced ROS generation in these cells is attenuated by DPI, an inhibitor of flavoenzymes, including Nox. [19][20][21] We therefore investigated whether BLT2-dependent, Nox-mediated ROS generation might contribute to LPS-induced IL-6 synthesis in mouse peritoneal macrophages. First, consistent with previous observations, we found that LPS induced ROS production in a manner sensitive to DPI or NAC, a free radical scavenger, in peritoneal macrophages (Figure 4a).…”

Section: Nox1-ros Signaling Functions Downstream Of Blt2 In Lpsinducementioning

confidence: 99%

MyD88–BLT2-dependent cascade contributes to LPS-induced interleukin-6 production in mouse macrophage

2015

View full text Add to dashboard Cite

Endotoxic responses to bacterial lipopolysaccharide (LPS) are triggered by Toll-like receptor 4 (TLR4) and involve the production of inflammatory mediators, including interleukin-6 (IL-6), by macrophages. The detailed mechanism of IL-6 production by macrophages in response to LPS has remained unclear, however. We now show that LPS induces IL-6 synthesis in mouse peritoneal macrophages via the leukotriene B 4 receptor BLT2. Our results suggest that TLR4-MyD88 signaling functions upstream of BLT2 and that the generation of reactive oxygen species (ROS) by NADPH oxidase 1 (Nox1) and consequent activation of the transcription factor nuclear factor (NF)-κB function downstream of BLT2 in this response. These results suggest that a TLR4-MyD88-BLT2-Nox1-ROS-NF-κB pathway contributes to the synthesis of IL-6 in LPS-stimulated mouse macrophages.

show abstract

“…In this process, STAT3 activation was necessary for NADPH oxidase 1 (Nox1) expression [Lee et al, 2012]. Cooperation of JAK1 and JAK3 contributed to Nox1 expression and ROS production stimulated by TLR2.…”

mentioning

confidence: 99%

Role of JAK2–STAT3 in TLR2‐mediated tissue factor expression

Park¹,

Lyu²,

Kim³

et al. 2013

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

Tissue factor (TF) is a core protein with an essential function in the coagulation cascade that maintains the homeostasis of the blood vessels. TF not only participates in neointima formation, but also causes the development of atherosclerosis. This study investigated the mechanism regulating TF expression in macrophages using Pam3 CSK4 , a TLR2 ligand. Pam3 CSK4 induced TF expression in two types of macrophages (Raw264.7 and BMDM), but not in TLR2 KO mice derived BMDM. Pam3 CSK4 induced TF expression was inhibited by pretreatment with pan-JAK inhibitor or JAK2 inhibitor AG490. JAK2 knock-down by siRNA inhibited Pam3 CSK4 induced TF expression. Pam3 CSK4 stimulated STAT3 phosphorylation (S727), while STAT3 knock-down by siRNA reduced Pam3 CSK4 induced TF expression. These results suggest that Pam3 CSK4 induced TF expression is regulated by the JAK2-STAT3 signaling pathway. Pam3 CSK4 , unlike increased TF expression, significantly decreased RGS2 expression, while RGS2 overexpression decreased Pam3 CSK4 induced TF expression. Inhibition of TF by RGS2 WT did not occur in mutants with flawed RGS domains. We also investigated the correlation between RGS2 and STAT3 phosphorylation. RGS2 knock-down elevated Pam3 CSK4 induced STAT3 phosphorylation, but RGS2 overexpression had the opposite effect on STAT3 phosphorylation. These results suggest that, while Pam3 CSK4 induced TF expression is regulated by JAK2-STAT3 signaling, RGS2 is a negative regulator targeted to STAT3.

show abstract

RGS2 is a negative regulator of STAT3-mediated Nox1 expression

Cited by 23 publications

References 39 publications

Single Nucleotide Polymorphisms in G Protein Signaling Pathway Genes in Preeclampsia

Single Nucleotide Polymorphisms in G Protein Signaling Pathway Genes in Preeclampsia

MyD88–BLT2-dependent cascade contributes to LPS-induced interleukin-6 production in mouse macrophage

Role of JAK2–STAT3 in TLR2‐mediated tissue factor expression

Contact Info

Product

Resources

About