Geniposide attenuates inflammatory response by suppressing P2Y14 receptor and downstream ERK1/2 signaling pathway in oxygen and glucose deprivation-induced brain microvascular endothelial cells

Li, Fanghe; Li, Weihong; Li, Xingguang; Li, Feng; Zhang, Linpeng; Wang, Bingce; Huang, Guangrui; Guo, Xiaojin; Wan, Liangqin; Liu, Yongqiang; Zhang, Sai; Kang, So Yeon; Ma, Jiabao

doi:10.1016/j.jep.2016.03.025

Cited by 52 publications

(27 citation statements)

References 32 publications

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“…11 P2Y activation has been showed to induce the downstream increase in phosphorylation of ERK and induce the release of proinflammatory cytokines such as IL-6, IL-8, MCP-1, IL-1β. 39,40 In our study, we found that ADP at high concentrations significantly induced the mRNA expression of VCAM-1 and ICAM-1, and induced a time-dependent increase in ERK1/2 phosphorylation. Thus, we hypothesized that ADP induced the expression of inflammatory factors by activating the ERK signaling pathway.…”

Section: Discussionsupporting

confidence: 55%

“…Different signal transduction pathways transduce the control of inflammation by P2Y receptors, including the mitogen‐activated protein kinases, ERK1/2, p38, and JNK . P2Y activation has been showed to induce the downstream increase in phosphorylation of ERK and induce the release of proinflammatory cytokines such as IL‐6, IL‐8, MCP‐1, IL‐1β . In our study, we found that ADP at high concentrations significantly induced the mRNA expression of VCAM‐1 and ICAM‐1, and induced a time‐dependent increase in ERK1/2 phosphorylation.…”

Section: Discussionsupporting

confidence: 51%

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Adenosine diphosphate–sensitive P2Y11 receptor inhibits endothelial cell proliferation by induction of cell cycle arrest in the S phase and induces the expression of inflammatory mediators

Chen

Xiao

Yang

et al. 2018

J of Cellular Biochemistry

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Extracellular adenosine diphosphate (ADP) mediates a wide range of physiological effects as an extracellular signaling molecule, including platelet aggregation, vascular tone, cell proliferation, and apoptosis by interacting with plasma membrane P2 receptors. However, the effect of ADP on cell proliferation was contradictory. In this study, we found that ADP significantly inhibited cell proliferation of human umbilical vein endothelial cells at high concentrations (50 to 100 µM). Treatment with ADP did not induce cell apoptosis but instead induced cell cycle arrest in the S phase, which may be partly due to the downregulation of cyclin B1. The inhibition of cell proliferation was blocked by suramin, a nonspecific antagonist of the P2 receptors, and high concentrations of ADP significantly upregulated the messenger RNA (mRNA) and protein expression of P2Y11 in endothelial cells. Moreover, the downregulation of P2Y11 by RNA interference reversed the inhibition of cell proliferation. In addition, ADP (100 µM) can induce the formation of cytosolic autophagy in endothelial cells and a rapid phosphorylation of extracellular signal regulated kinase (ERK) 1/2, which is a canonical signal molecule downstream of P2Y receptors, accompanied by a mRNA expression of proinflammatory cytokines such as intercellular adhesion molecule 1 and vascular cell adhesion molecule 1. Taken together, our study excludes a mechanism for extracellular ADP impairing endothelial cells proliferation via P2Y11 receptor by downregulating cyclin B1 and arresting cell cycle at the S phase, besides, ADP induces cell autophagy and mRNA expression of inflammatory cytokines, whether it is mediated by Erk signaling pathways needs further studies to confirm.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionsupporting

confidence: 51%

Adenosine diphosphate–sensitive P2Y11 receptor inhibits endothelial cell proliferation by induction of cell cycle arrest in the S phase and induces the expression of inflammatory mediators

Chen

Xiao

Yang

et al. 2018

J of Cellular Biochemistry

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“…However, the exact mechanisms that sensitize CMECs to H̸R injury remain incompletely understood and the endogenous mechanisms that may regulate the disassociation between TLR4 and CMEC H̸R injury are not known. Previous studies revealed that the activity of p-ERK1̸2 was involved in the inflammatory injury of brain microvascular endothelial cells caused by mock ischemic treatment (31), and its participation in inducing apoptosis under hypoxic conditions was also verified (32,33). Moreover, the pro-inflammatory and -apoptotic patterns of p-p38 MAPK and p-JNK activation in the ischemic endothelium have also been extensively investigated (10)(11)(12)(13)(14)(15)27,34).…”

Section: Discussionmentioning

confidence: 91%

RP105 ameliorates hypoxia̸reoxygenation injury in cardiac microvascular endothelial cells by suppressing TLR4̸MAPKs̸NF-κB signaling

et al. 2018

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The radioprotective 105 kDa protein (RP105) has been implicated in the pathological process of multiple cardiovascular diseases through its functional and physical interactions with Toll‑like receptor 4 (TLR4). However, the effects of RP105 on cardiac microvascular endothelial cells (CMECs) in response to hypoxia̸reoxygenation (H̸R) injury have not been extensively investigated. The aim of the present study was to elucidate the potential roles of RP105 in the protection of CMECs against H̸R injury, and investigate the underlying mechanisms. CMECs isolated from Sprague‑Dawley rats were transduced with adenoviral vectors encoding RP105 or green fluorescent protein (GFP). At 48 h post‑transfection, CMECs were subjected to hypoxia for 4 h and reoxygenation for 2 h (H̸R) to simulate the in vivo ischemia̸reperfusion model. The mRNA and protein levels of RP105 were detected by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. The effects of RP105 on CMEC proliferation, migration and apoptosis were measured by GFP‑8, Transwell chamber and flow cytometry assays, respectively. The secretion of interleukin (IL)‑6 and tumor necrosis factor (TNF)‑α in the culture medium was measured by ELISA. Moreover, the expression level of TLR4, p38 mitogen‑activated protein kinase (MAPK), extracellular-signal-regulated kinase 1̸2, c-Jun N-terminal kinase, nuclear factor (NF)‑κB̸p65, IL‑6, TNF‑α and intercellular adhesion melecule‑1 was evaluated by western blot analysis. The results demonstrated that RP105 was minimally expressed in CMECs subjected to H̸R injury. Overexpression of RP105 via adenoviral vectors was able to significantly protect CMECs against H̸R injury, as evidenced by the promotion of cell proliferation and migration, as well as the amelioration of inflammation and apoptosis. These beneficial effects were at least partly mediated through inhibition of TLR4̸MAPKs̸NF‑κB signaling. Therefore, RP105 may be a promising candidate for prevention against CMECs‑associated H̸R injury.

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“…Geniposide is an iridoid glycoside compound extracted from Gardenia jasminoides fruit, which is a traditional Chinese herb that is used to treat vitiligo. Geniposide possesses anti‐inflammatory properties, enhances melanogenesis and exerts antioxidant effects . However, the antioxidant actions of geniposide in melanocytes and the underlying mechanisms remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Geniposide prevents H₂ O₂ -induced oxidative damage in melanocytes by activating the PI3K-Akt signalling pathway

Kong

Zhang

et al. 2018

Clin Exp Dermatol

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Geniposide attenuates inflammatory response by suppressing P2Y14 receptor and downstream ERK1/2 signaling pathway in oxygen and glucose deprivation-induced brain microvascular endothelial cells

Cited by 52 publications

References 32 publications

Adenosine diphosphate–sensitive P2Y11 receptor inhibits endothelial cell proliferation by induction of cell cycle arrest in the S phase and induces the expression of inflammatory mediators

Adenosine diphosphate–sensitive P2Y11 receptor inhibits endothelial cell proliferation by induction of cell cycle arrest in the S phase and induces the expression of inflammatory mediators

RP105 ameliorates hypoxia̸reoxygenation injury in cardiac microvascular endothelial cells by suppressing TLR4̸MAPKs̸NF-κB signaling

Geniposide prevents H₂ O₂ -induced oxidative damage in melanocytes by activating the PI3K-Akt signalling pathway

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Geniposide attenuates inflammatory response by suppressing P2Y14 receptor and downstream ERK1/2 signaling pathway in oxygen and glucose deprivation-induced brain microvascular endothelial cells

Cited by 52 publications

References 32 publications

Adenosine diphosphate–sensitive P2Y11 receptor inhibits endothelial cell proliferation by induction of cell cycle arrest in the S phase and induces the expression of inflammatory mediators

Adenosine diphosphate–sensitive P2Y11 receptor inhibits endothelial cell proliferation by induction of cell cycle arrest in the S phase and induces the expression of inflammatory mediators

RP105 ameliorates hypoxia̸reoxygenation injury in cardiac microvascular endothelial cells by suppressing TLR4̸MAPKs̸NF-κB signaling

Geniposide prevents H2 O2 -induced oxidative damage in melanocytes by activating the PI3K-Akt signalling pathway

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Geniposide prevents H₂ O₂ -induced oxidative damage in melanocytes by activating the PI3K-Akt signalling pathway