Soluble epoxide hydrolase inhibitor attenuates BBB disruption and neuroinflammation after intracerebral hemorrhage in mice

Tian, Ye; Yuan, Xiao; Wang, Yao; Wu, Qiao; Fang, Yongkang; Zhou, Zhuxian; Song, Guini; Xu, Li; Wang, Wei; Xie, Mingxing

doi:10.1016/j.neuint.2021.105197

Cited by 18 publications

(16 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…11, 12‐EET can induce more robust tube formation by markedly increasing VEGF‐A and bFGF expression in myocardial infarction 22 . EETs also encourage the generation of angiogenesis transcription factors through the HIF‐1α pathway, and increase HIF‐1α‐DNA‐binding activity to improve the resistance of myocytes to acute ischemia–reperfusion 23–27 …”

Section: Introductionmentioning

confidence: 99%

“…22 EETs also encourage the generation of angiogenesis transcription factors through the HIF-1α pathway, and increase HIF-1α-DNAbinding activity to improve the resistance of myocytes to acute ischemia-reperfusion. [23][24][25][26][27] However, soluble epoxide hydrolase (sEH) can rapidly hydrolyze EETs to bio-inactive dihydroxyeicosatrienoic acids (DHETs) in vivo, so the half-life of EETs is short, which limits the pharmacological efficacy through EETs administration. 28 Thus, stabilizing endogenous EETs by sEH inhibitor (sEHi) becomes a candidate strategy.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Targeting soluble epoxide hydrolase promotes osteogenic–angiogenic coupling via activating SLIT3/HIF‐1α signalling pathway

Chen

et al. 2023

Cell Proliferation

View full text Add to dashboard Cite

Type H vessels have recently been identified to modulate osteogenesis. Epoxyeicostrioleic acids (EETs) have an essential contribution to vascular homeostasis. However, whether increased EETs with soluble epoxide hydrolase (sEH) inhibitor TPPU enhance the coupling of angiogenesis and osteogenesis remains largely unknown. The effects of TPPU on cross‐talk between co‐cultured human umbilical vein endothelial cells (HUVECs) and human dental pulp stem cells (hDPSCs), and on long bone growth and calvarial defect repair in mice were investigated in vitro and in vivo. TPPU enhanced osteogenic differentiation of co‐cultured HUVECs and hDPSCs in vitro and increased type H vessels, and long bone growth and bone repair of calvarial defect. Mechanistically, TPPU promoted cell proliferation and angiogenesis, reclined cell apoptosis, and significantly increased CD31hiEMCNhi endothelial cells (ECs) and SLIT3 and HIF‐1α expression levels in co‐cultured HUVECs and hDPSCs. Knockdown of Slit3 in hDPSCs or Hif‐1α in HUVECs impaired the formation of CD31hiEMCNhi ECs and reversed TPPU‐induced osteogenesis. We defined a previously unidentified effect of TPPU coupling angiogenesis and osteogenesis. TPPU induced type H vessels by upregulating the expression of hDPSCs‐derived SLIT3, which resulted in the activation of ROBO1/YAP1/HIF‐1α signalling pathway in ECs. Targeting metabolic pathways of EETs represents a new strategy to couple osteogenesis and angiogenesis, sEH is a promising therapeutic target for bone regeneration and repair.

show abstract

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Targeting soluble epoxide hydrolase promotes osteogenic–angiogenic coupling via activating SLIT3/HIF‐1α signalling pathway

Chen

et al. 2023

Cell Proliferation

View full text Add to dashboard Cite

show abstract

“…EETs/sEHi have the property of promoting the regeneration of different tissues 34 . EETs have been shown to have inflammatory protective effects in various types of arthritisand neuritis 35 , 36 . TPPU stabilizes the level of EETs and exerts an anti-inflammatory effect by reducing the expression of NLRP3 inflammasome-related molecules under LPS stimulation 37 and inhibiting NF-kB activation in mouse macrophages 38 .…”

Section: Discussionmentioning

confidence: 99%

TPPU inhibits inflammation-induced excessive autophagy to restore the osteogenic differentiation potential of stem cells and improves alveolar ridge preservation

Dang

Chen

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Inflammation-induced autophagy is a double-edged sword. Dysfunction of autophagy impairs the differentiation capacity of mesenchymal stem cells and enhances inflammation-induced bone loss. Tooth extraction with periodontal and/or endodontic lesions exacerbates horizontal and vertical resorption of alveolar bone during the healing period. Alveolar socket preservation (ASP) procedure following tooth extraction has important clinical implications for future prosthodontic treatments. Studies have shown that epoxyeicosatrienoic acids (EETs) have significant anti-inflammatory effects and participate in autophagy. However, whether EETs can minimize alveolar bone resorption and contribute to ASP by regulating autophagy levels under inflammatory conditions remain elusive. Here, we figured out that LPS-induced inflammatory conditions increased the inflammatory cytokine and inhibited osteogenic differentiation of human dental pulp stem cells (hDPSCs), and led to excessive autophagy of hDPSCs. Moreover, we identified that increased EETs levels using TPPU, a soluble epoxide hydrolase inhibitor, reversed these negative outcomes. We further demonstrated the potential of TPPU to promote early healing of extraction sockets and ASP, and speculated that it was related to autophagy. Taken together, these results suggest that targeting inhibition of soluble epoxide hydrolase using TPPU plays a protective role in the differentiation and autophagy of mesenchymal stem cells and provides potential feasibility for applying TPPU for ASP, especially under inflammatory conditions.

show abstract

“…In intracerebral hemorrhage mouse and ischemic injury rats, TPPU suppresses inflammation and secondary injuries and promotes functional recovery by alleviating BBB damage and increasing the regulation of microglial cell polarization. 19,30 sEH inhibition might also attenuate the progression of BBB injury in diabetic mice via AMPK/heme oxygenase-1 (HO-1) pathway activation. 31 In this study, brain edema and BBB permeability could be induced by DAI and OGD and aggravated by hyperglycemia in vivo and vitro.…”

Section: Seh Disrupted Of the Integrity Of The Bbb Through The Nf-κb ...mentioning

confidence: 99%

Hyperglycemia disrupted the integrity of the blood‐brain barrier following diffuse axonal injury through the sEH/NF‐κB pathway

Wei,

Xing,

Huang

et al. 2023

Immunity Inflam & Disease

View full text Add to dashboard Cite

ObjectivesWe aimed to investigate the role of soluble epoxide hydrolase for hyperglycemia induced‐disruption of blood‐brain barrier (BBB) integrity after diffuse axonal injury (DAI).MethodsRat DAI hyperglycemia model was established by a lateral head rotation device and intraperitoneal injection of 50% glucose. Glial fibrillary acidic protein, ionized calcium‐binding adapter molecule‐1, β‐amyloid precursor protein, neurofilament light chain, and neurofilament heavy chain was detected by immunohistochemistry. Cell apoptosis was examined by terminal deoxynucleotidyl transferase nick‐end labeling (TUNEL) assay. The permeability of blood‐brain barrier (BBB) was assessed by expression of tight junction proteins, leakage of Evans blue and brain water content. The soluble epoxide hydrolase (sEH) pathway was inhibited by 1‐trifluoromethoxyphenyl‐3‐(1‐propionylpiperidin‐4‐yl) urea (TPPU) and the nuclear transcription factor kappa B (NF‐κB) pathway was inhibited by pyrrolidine dithiocarbamate and activated by phorbol‐12‐myristate‐13‐acetate in vivo and/or vitro, respectively. The inflammatory factors were detected by enzyme‐linked immunosorbent assay.ResultsHyperglycemia could exacerbate axonal injury, aggravate cell apoptosis and glial activation, worsen the loss of BBB integrity, increase the release of inflammatory factors, and upregulate the expression of sEH and NF‐κB. Inhibition of sEH could reverse all these damages and protect BBB integrity by upregulating the expression of tight junction proteins and downregulating the levels of inflammatory factors in vivo and vitro, while the agonist of NF‐κB pathway abrogated the protective effects of TPPU on BBB integrity in vitro.ConclusionssEH was involved in mediating axonal injury induced by hyperglycemia after DAI by disrupting BBB integrity through inducing inflammation via the NF‐κB pathway.

show abstract

Soluble epoxide hydrolase inhibitor attenuates BBB disruption and neuroinflammation after intracerebral hemorrhage in mice

Cited by 18 publications

References 51 publications

Targeting soluble epoxide hydrolase promotes osteogenic–angiogenic coupling via activating SLIT3/HIF‐1α signalling pathway

Targeting soluble epoxide hydrolase promotes osteogenic–angiogenic coupling via activating SLIT3/HIF‐1α signalling pathway

TPPU inhibits inflammation-induced excessive autophagy to restore the osteogenic differentiation potential of stem cells and improves alveolar ridge preservation

Hyperglycemia disrupted the integrity of the blood‐brain barrier following diffuse axonal injury through the sEH/NF‐κB pathway

Contact Info

Product

Resources

About