<i>Retracted</i>: Protective effects of Progranulin against focal cerebral ischemia‐reperfusion injury in rats by suppressing endoplasmic reticulum stress and NF‐κB activation in reactive astrocytes

Shu, Qing; Fan, Hua; Li, Shijun; Zhou, Dan; Ma, Wei; Zhao, Xiaoyan; Yan, Jize; Wu, Gang

doi:10.1002/jcb.26790

Cited by 23 publications

(6 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even during reperfusion, ER stress-related protein levels were continuously elevated, suggesting the persistent activation of ER stress. To our knowledge, studies on I/R-induced ER stress in the brain have focused mainly on neuronal cells (18)(19)(20) and astrocytes (21,22) in vitro and in vivo. To date, the mechanisms responsible for ER stress associated with I/R-induced BBB disruption have remained unclear.…”

Section: Discussionmentioning

confidence: 99%

Cilostazol ameliorates ischemia/reperfusion‐induced tight junction disruption in brain endothelial cells by inhibiting endoplasmic reticulum stress

et al. 2019

View full text Add to dashboard Cite

Endoplasmic reticulum (ER) stress is essential for brain ischemia/reperfusion (I/R) injury. However, whether it contributes to I/R‐induced blood‐brain barrier (BBB) injury remains unclear, cilostazol exerts protective effects toward I/R‐induced BBB injury, with unclear mechanisms. This study explored the potential role of ER stress in I/R‐induced endothelial cell damage and determined whether the therapeutic potential of cilostazol, with respect to I/R‐induced endothelial cell damage, is related to inhibition of ER stress. We found that exposing brain endothelial cells (bEnd.3) to oxygen‐glucose deprivation/reoxygenation (OGD/R) significantly activated ER stress and diminished the barrier function of cell monolayers; treatment with the ER stress inhibitor 4‐phenylbutyric acid (4‐PBA) or cilostazol prevented OGD/R‐induced ER stress and preserved barrier function. Furthermore, OGD/R induced the expression and secretion of matrix metalloproteinase‐9 and nuclear translocation of phosphorylated NF‐κB. These changes were partially reversed by 4‐PBA or cilostazol treatment. In vivo, 4‐PBA or cilostazol significantly attenuated I/R‐induced ER stress and ameliorated Evans blue leakage and tight junction loss. These results demonstrate that I/R‐induced ER stress participates in BBB disruption. Targeting ER stress could be a useful strategy to protect the BBB from ischemic stroke, and cilostazol is a promising therapeutic agent for this process.—Nan, D., Jin, H., Deng, J., Yu, W., Liu, R., Sun, W., Huang, Y. Cilostazol ameliorates ischemia/reperfusion‐induced tight junction disruption in brain endothelial cells by inhibiting endoplasmic reticulum stress. FASEB J. 33,10152–10164 (2019). http://www.fasebj.org

show abstract

Section: Discussionmentioning

confidence: 99%

Cilostazol ameliorates ischemia/reperfusion‐induced tight junction disruption in brain endothelial cells by inhibiting endoplasmic reticulum stress

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The pathophysiological mechanisms of cerebral I/R injury are very complex [ 3 ] and include energy metabolism impairment, oxidative stress, glutamate/neurotoxin release, calcium-overload, inflammation, apoptosis [ 4 ], and autophagy [ 5 ]. To date, apoptosis has been shown to play a role in cerebral I/R injury [ 6 – 9 ]; inhibition of apoptosis is a potential therapeutic target in stroke patients.…”

Section: Introductionmentioning

confidence: 99%

Xingnaojing Injection Protects against Cerebral Ischemia Reperfusion Injury via PI3K/Akt‐Mediated eNOS Phosphorylation

Zhang

Zhai

et al. 2018

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Xingnaojing (XNJ) injection, derived from traditional Chinese medicine formulation, has a protective effect against stroke, but the underlying mechanism is unclear, which severely limited its clinical application. This research aims to elucidate the role and mechanism of XNJ in reducing cerebral ischemic reperfusion (I/R) injury. Rats received 2 h cerebral ischemia followed by reperfusion of 24 h and were intraperitoneally given 5, 10, or 15 ml/kg XNJ 24 h before ischemia and at the onset of reperfusion, respectively. TTC staining, HE staining, and neurological score were implied to evaluate the effectiveness of XNJ. The protein expressions of PI3K/Akt and eNOS signaling were measured. Experiments were further performed in human brain microvascular endothelial cells (HBMECs) to investigate the protective mechanisms of XNJ. HBMECs were subjected to 3 h oxygen and glucose deprivation following 24 h of reoxygenation (OGD) to mimic cerebral I/R in vitro. PI3K inhibitor LY294002 was added with or without the preconditioning of XNJ. Multiple methods including western blot, immunofluorescence, DAPI staining, JC-1, and flow cytometry were carried out to evaluate the effect of XNJ on HBMECs. XNJ could improve rat cerebral ischemic injury and OGD induced HBMECs apoptosis. In vivo and in vitro researches indicated that the mechanism might be relevant to the activation of PI3K/Akt/eNOS signaling.

show abstract

“…PGRN expression in airway epithelial cells inhibited cigarette smoke-induced apoptosis through the regulation of ERS (46). In cerebral ischemia/reperfusion injury, PGRN reduced neuronal apoptosis by mitigating ERS in the reactive astrocytes (47). Because there is substantial evidence for influenza virus induction of ERS and apoptosis (48-50), we then explored the involvement of ERS in the apoptosis during coinfection.…”

Section: Discussionmentioning

confidence: 99%

Progranulin Decreases Susceptibility to Streptococcus pneumoniae in Influenza and Protects against Lethal Coinfection

Wang

Yuan

Wang

et al. 2019

The Journal of Immunology

View full text Add to dashboard Cite

Streptococcus pneumoniae coinfection is a major cause of mortality in influenza pandemics. Growing evidence shows that uncontrolled immune response results in severe tissue damage and thereby promotes death in coinfection. Progranulin (PGRN) is widely expressed in immune and epithelial cells and exerts anti-inflammatory role in many diseases. We found that PGRN levels were significantly elevated in clinical influenza/S. pneumoniae-coinfected patients. C57BL/6 wild-type (WT) and PGRN-deficient (PGRN 2/2 ) mice were infected with influenza virus PR8 and then superchallenged with S. pneumoniae serotype 19F. Coinfected PGRN 2/2 mice showed increased mortality and weight loss compared with WT mice. PGRN deficiency led to increased bacterial loads in lungs without altering influenza virus replication, suggesting a role of PGRN in decreasing postinfluenza susceptibility to S. pneumoniae coinfection. Administration of recombinant PGRN improved survival of WT and PGRN 2/2 mice in lethal coinfection. Additionally, loss of PGRN resulted in aggravated lung damage along with massive proinflammatory cytokine production and immune cell infiltration during coinfection. Endoplasmic reticulum stress (ERS) during influenza, and coinfection was strongly induced in PGRN 2/2 mice that subsequently activated apoptosis signaling pathways. Treatment of recombinant PGRN or inhibition of ERS by 4-phenylbutyrate decreased apoptosis and bacterial loads in lungs of coinfected mice. These results suggest that PGRN decreases postinfluenza susceptibility to S. pneumoniae coinfection via suppressing ERS-mediated apoptosis. Impaired bacterial clearance and increased lung inflammation are associated with the lethal outcome of coinfected PGRN 2/2 mice. Our study provides therapeutic implication of PGRN to reduce morbidity and mortality in influenza/S. pneumoniae coinfection.

show abstract

Retracted: Protective effects of Progranulin against focal cerebral ischemia‐reperfusion injury in rats by suppressing endoplasmic reticulum stress and NF‐κB activation in reactive astrocytes

Cited by 23 publications

References 41 publications

Cilostazol ameliorates ischemia/reperfusion‐induced tight junction disruption in brain endothelial cells by inhibiting endoplasmic reticulum stress

Cilostazol ameliorates ischemia/reperfusion‐induced tight junction disruption in brain endothelial cells by inhibiting endoplasmic reticulum stress

Xingnaojing Injection Protects against Cerebral Ischemia Reperfusion Injury via PI3K/Akt‐Mediated eNOS Phosphorylation

Progranulin Decreases Susceptibility to Streptococcus pneumoniae in Influenza and Protects against Lethal Coinfection

Contact Info

Product

Resources

About