Regulator of G-protein signaling 5 protects cardiomyocytes against apoptosis during in vitro cardiac ischemia-reperfusion in mice by inhibiting both JNK1/2 and P38 signaling pathways

Wang, Zhiqiang; Huang, He; He, Wangwei; Kong, Bin; Hu, Hexiang; Yang, Fan; Liao, Junlin; Wang, Lei; Yang, Minghui; Liu, Wanli; Xiong, Xiaoju; Peng, Jianye; Xiao, Yali; Huang, Dan; Quan, Dajun; Li, Qi; Xiong, Liang; Zhong, Peng; Wang, Guangji

doi:10.1016/j.bbrc.2016.03.114

Cited by 24 publications

(24 citation statements)

References 28 publications

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“…Indeed, RGS5 has previously been shown to be involved in PDGF-induced ERK phosphorylation (23). In addition, loss of RGS5 has been shown to negatively regulate signaling pathways in other systems [e.g., it has been shown that loss of RGS5 inhibits JNK1/2 and p38 signaling, leading to markedly reversed ischemiareperfusion-induced cardiomyocyte apoptosis (39)]. However, further studies are needed to dissect the implications of RGS5 on the downstream signaling pathways that are involved in pericyte detachment mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Regulator of G‐protein signaling 5 regulates the shift from perivascular to parenchymal pericytes in the chronic phase after stroke

et al. 2019

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Poststroke recovery requires multiple repair mechanisms, including vascular remodeling and blood‐brain barrier (BBB) restoration. Brain pericytes are essential for BBB repair and angiogenesis after stroke, but they also give rise to scar‐forming platelet‐derived growth factor receptor β (PDGFR‐β)‐expressing cells. However, many of the molecular mechanisms underlying this pericyte response after stroke still remain unknown. Regulator of G‐protein signaling 5 (RGS5) has been associated with pericyte detachment from the vascular wall, but whether it regulates pericyte function and vascular stabilization in the chronic phase of stroke is not known. Using RGS5‐knockout (KO) mice, we study how loss of RGS5 affects the pericyte response and vascular remodeling in a stroke model at 7 d after ischemia. Loss of RGS5 leads to a shift toward an increase in the number of perivascular pericytes and reduction in the density of parenchymal PDGFR‐β‐expressing cells associated with normalized PDGFR‐β activation after stroke. The redistribution of pericytes resulted in higher pericyte coverage, increased vascular density, preservation of vessel lengths, and a significant reduction in vascular leakage in RGS5‐KO mice compared with controls. Our study demonstrates RGS5 in pericytes as an important target to enhance vascular remodeling.—Roth, M., Gaceb, A., Enström, A., Padel, T., Genové, G., Özen, I., Paul, G. Regulator of G‐protein signaling 5 regulates the shift from perivascular to parenchymal pericytes in the chronic phase after stroke. FASEB J. 33, 8990–8998 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Regulator of G‐protein signaling 5 regulates the shift from perivascular to parenchymal pericytes in the chronic phase after stroke

et al. 2019

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“…RGS5 is among the simplest members of the superfamily as it contains only an RGS box, the motif common to all RGS proteins mediating binding to G␣ (13), but no other well defined domains. RGS5 is expressed constitutively in relatively few tissues in mice, including vascular and bronchial smooth muscle (14,15) and cardiomyocytes (16). Rgs5 Ϫ/Ϫ mice at baseline were underweight and hypotensive compared with controls, suggesting critical roles for RGS5 in metabolism and cardiovascular homeostasis (17).…”

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confidence: 99%

Regulator of G protein signaling 5 restricts neutrophil chemotaxis and trafficking

Chan

Ren

Jude

et al. 2018

Journal of Biological Chemistry

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Neutrophils are white blood cells that are mobilized to damaged tissues and to sites of pathogen invasion, providing the first line of host defense. Chemokines displayed on the surface of blood vessels promote migration of neutrophils to these sites, and tissue- and pathogen-derived chemoattractant signals, including -formylmethionylleucylphenylalanine (fMLP), elicit further migration to sites of infection. Although nearly all chemoattractant receptors use heterotrimeric G proteins to transmit signals, many of the mechanisms lying downstream of chemoattractant receptors that either promote or limit neutrophil motility are incompletely defined. Here, we show that regulator of G protein signaling 5 (RGS5), a protein that modulates G protein activity, is expressed in both human and murine neutrophils. We detected significantly more neutrophils in the airways of mice than WT counterparts following acute respiratory virus infection and in the peritoneum in response to injection of thioglycollate, a biochemical proinflammatory stimulus. RGS5-deficient neutrophils responded with increased chemotaxis elicited by the chemokines CC motif chemokine ligand 1 (CXCL1), CXCL2, and CXCL12 but not fMLP. Moreover, adhesion of these cells was increased in the presence of both CXCL2 and fMLP. In summary, our results indicate that RGS5 deficiency increases chemotaxis and adhesion, leading to more efficient neutrophil mobilization to inflamed tissues in mice. These findings suggest that RGS5 expression and activity in neutrophils determine their migrational patterns in the complex microenvironments characteristic of inflamed tissues.

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“…Functional study indicated that GPR18, the most abundantly overexpressed orphan GPCR in all melanoma metastases, is constitutively active and inhibits apoptosis, suggesting that GPR18 plays an important role in cancer cell survival and may be considered as potential anticancer targets in metastatic melanoma [ 40 ]. In addition, R4 RGS proteins, as the suppressors of GPCR signal, appear to be negatively associated with cancer proliferation and progression ,and regulate the pro-apoptotic factors [ 23 , 24 , 36 – 38 , 41 ]. In our study, we found that overexpression of RGS4 inhibited melanoma cell proliferation and promoted apoptosis in melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

Regulator of G protein signaling 4 inhibits human melanoma cells proliferation and invasion through the PI3K/AKT signaling pathway

et al. 2017

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Melanoma is a tumor produced by skin melanocytes, which has a high metastatic rate and poor prognosis. So far, plenty of work has been done on melanoma, but mechanisms underlying melanoma development have not been fully elucidated. Here we identified regulator of G protein signaling 4(RGS4) as novel therapeutic target for malignant melanoma and its regulating effect on melanoma. We found that endogenous RGS4 expression was much lower in melanoma tissues and cells. In A375 cell line with low endogenous RGS4 expression, the function of RGS4 was detected by up-regulation its expression with pcDNA3.1-RGS4 and knockdown its expression with siRNA. Our results showed that RGS4 could significantly reduce the proliferation, migration and invasion of melanoma cells. RGS4 is an important regulator for the apoptosis of melanocyte, and the apoptosis rate is significantly decreased in low RGS4 enviroment. RGS4 induced non-activation of PI3K/AKT pathway, resulting in decreased expression of E2F1 and Cyclin D1, thus constraining cell proliferation and invasion. These results were further confirmed in M14 cell lines. Collectively, our findings show that RGS4 plays an important role in multiple cellular functions of melanoma development and is valuable to be a therapeutic target.

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Regulator of G-protein signaling 5 protects cardiomyocytes against apoptosis during in vitro cardiac ischemia-reperfusion in mice by inhibiting both JNK1/2 and P38 signaling pathways

Cited by 24 publications

References 28 publications

Regulator of G‐protein signaling 5 regulates the shift from perivascular to parenchymal pericytes in the chronic phase after stroke

Regulator of G‐protein signaling 5 regulates the shift from perivascular to parenchymal pericytes in the chronic phase after stroke

Regulator of G protein signaling 5 restricts neutrophil chemotaxis and trafficking

Regulator of G protein signaling 4 inhibits human melanoma cells proliferation and invasion through the PI3K/AKT signaling pathway

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