RACK1 upregulation induces neuroprotection by activating the IRE1-XBP1 signaling pathway following traumatic brain injury in rats

Ni, Haibo; Qin, Rui; Xu, Yitian; Jing-ci, Zhu; Gao, Fan; Dang, Baoqi; Li, Di; Gao, Rong; Chen, Gang

doi:10.1016/j.expneurol.2018.03.003

Cited by 28 publications

(31 citation statements)

References 37 publications

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“…Our previous study demonstrated that OVA challenge significantly induced EMT process in airway epithelium via up‐regulation of TGF‐β1/RACK1, which is consistent with the report that knockdown RACK1 significantly inhibits the activation of TGF‐β/Smad signalling pathway in renal fibrosis . Moreover, it has been confirmed that RACK1 is required for regulating apoptosis although the role of RACK1 in regulating apoptosis remains controversial . However, the dual role and the potential mechanism of RACK1 in regulating airway epithelial apoptosis and EMT remain unclear.…”

Section: Introductionsupporting

confidence: 86%

“…Functioned as the downstream target gene of TGF‐β1, RACK1 has been implicated in the pathogenesis of fibrosis and apoptosis, but its involvement in the development of airway epithelial damage and repair remains largely unknown. In the present study, we have demonstrated an overexpression of RACK1 in a mouse model of allergic airway inflammation induced by OVA challenge and in TGF‐β1‐induced airway epithelial apoptosis and EMT model.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, RACK1 has been found to act as a scaffold protein for PKC and interact with a variety of proteins in the regulation of apoptosis and fibrosis . To explain the relationship between RACK1 and TGF‐β1‐induced apoptosis and EMT process, we performed a mechanistic study to determine whether inhibition of RACK1 expression significantly attenuated TGF‐β1‐induced apoptosis and EMT in airway epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

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Dual role of RACK1 in airway epithelial mesenchymal transition and apoptosis

Liu

Zhou

et al. 2020

J Cellular Molecular Medi

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Airway epithelial apoptosis and epithelial mesenchymal transition (EMT) are two crucial components of asthma pathogenesis, concomitantly mediated by TGF‐β1. RACK1 is the downstream target gene of TGF‐β1 shown to enhancement in asthma mice in our previous study. Balb/c mice were sensitized twice and challenged with OVA every day for 7 days. Transformed human bronchial epithelial cells, BEAS‐2B cells were cultured and exposed to recombinant soluble human TGF‐β1 to induced apoptosis (30 ng/mL, 72 hours) and EMT (10 ng/mL, 48 hours) in vitro, respectively. siRNA and pharmacological inhibitors were used to evaluate the regulation of RACK1 protein in apoptosis and EMT. Western blotting analysis and immunostaining were used to detect the protein expressions in vivo and in vitro. Our data showed that RACK1 protein levels were significantly increased in OVA‐challenged mice, as well as TGF‐β1‐induced apoptosis and EMT of BEAS‐2B cells. Knockdown of RACK1 (siRACK1) significantly inhibited apoptosis and decreased TGF‐β1 up‐regulated EMT related protein levels (N‐cadherin and Snail) in vitro via suppression of JNK and Smad3 activation. Moreover, siSmad3 or siJNK impaired TGF‐β1‐induced N‐cadherin and Snail up‐regulation in vitro. Importantly, JNK gene silencing (siERK) also impaired the regulatory effect of TGF‐β1 on Smad3 activation. Our present data demonstrate that RACK1 is a concomitant regulator of TGF‐β1 induces airway apoptosis and EMT via JNK/Smad/Snail signalling axis. Our findings may provide a new insight into understanding the regulation mechanism of RACK1 in asthma pathogenesis.

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Section: Introductionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Dual role of RACK1 in airway epithelial mesenchymal transition and apoptosis

Liu

Zhou

et al. 2020

J Cellular Molecular Medi

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“…A focal cortical contusion injury model induced by the weight-drop method was used to cause brain trauma, as described in our previous study (Ni et al, 2018). Briefly, general anesthesia was induced with 4% chloral hydrate (400 mg/kg, intraperitoneal injection).…”

Section: Methodsmentioning

confidence: 99%

“…Neurological function was assessed with the previously described modified Garcia scoring system at 72 h after TBI induction by an investigator who was blinded to the experimental design (Ni et al, 2018). The assessment consisted of seven tests covering spontaneous activity, axial sensation, vibrissae proprioception, lateral turning, symmetry of limb movement, forelimb walking, climbing, and grabbing.…”

Section: Methodsmentioning

confidence: 99%

2-BFI Provides Neuroprotection Against Inflammation and Necroptosis in a Rat Model of Traumatic Brain Injury

Qin

Lin

et al. 2019

Front. Neurosci.

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Inflammation and programmed necrosis (necroptosis) are the two hallmark pathological changes after traumatic brain injury (TBI) that contribute to aggravated brain damage. 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) has been shown to exert both anti-inflammatory and programmed cell death effects. Therefore, the aim of the present study was to evaluate the potential beneficial effects of 2-BFI in a rat model of TBI induced by a weight-drop device. 2-BFI or vehicle was given via intraperitoneal injection starting at 30 min post trauma and then twice daily for three consecutive days. Following a neurofunctional test at 72 h after injury, histological, molecular, and immunohistochemistry analyses were performed on the pericontusional areas of the brain. 2-BFI treatment significantly attenuated neurological deficits, brain edema and blood-brain barrier permeability after TBI. Also, treatment with 2-BFI significantly reduced microglial activation, neutrophil infiltration, and proinflammatory cytokine interleukin (IL)-1β secretion, which is related to nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation after TBI. In addition, 2-BFI treatment markedly reduced cortical tissue loss as well as repressed TBI-induced increases in necroptosis and necroptosis-associated proteins, including receptor-interacting protein (RIP1), RIP3, and mixed linkage kinase domain-like (MLKL) in the pericontusional brain tissue. Taken together, these findings indicate that 2-BFI may be an effective neuroprotectant after brain trauma and warrants further study.

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Tetrandrine alleviates inflammation and neuron apoptosis in experimental traumatic brain injury by regulating the IRE1α/JNK/CHOP signal pathway

Liu

et al. 2022

Brain and Behavior

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Aim:The aim of this study was to investigate the therapeutic roles of Tetrandrine (TET) on traumatic brain injury (TBI) and the underlying mechanism. Method: Traumatic injury model of hippocampal neurons and TBI mouse model were established to evaluate the therapeutic effects. The expression of neuron-specific enolase (NSE), Caspase 3, and Caspase 12 was detected by immunofluorescence. The expression of TNF-α, NF-κB, TRAF1, ERS markers (GADD34 and p-PERK), IRE1α, CHOP, JNK, and p-JNK were evaluated by western blot. Flow cytometry was used to determine the apoptosis of neurons. Brain injury was assessed by Garcia score, cerebral water content, and Evan blue extravasation test. Hematoxylin and eosin staining was used to determine the morphological changes of hippocampal tissue. Apoptosis was assessed by TUNEL staining. Result: In traumatic injury model of hippocampal neurons, TET downregulated NSE, TNF-α, NF-κB, TRAF1, GADD34, p-PERK, IRE1α, CHOP, and p-JNK expression. TET reduced Caspase 3 and Caspase 12 cleavage. Apoptosis rate was inhibited by the introduction of TET. TET improved the Garcia neural score, decreased the cerebral water content and Evans blue extravasation, and reduced NSE, TNF-α, NF-κB, TRAF1, IRE1α, CHOP, and p-JNK expression in mice with TBI, which was significantly reversed by Anisomycin, a JNK selective activator. Conclusion: TET alleviated inflammation and neuron apoptosis in experimental TBI by regulating the IRE1α/JNK/CHOP signal pathway.

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RACK1 upregulation induces neuroprotection by activating the IRE1-XBP1 signaling pathway following traumatic brain injury in rats

Cited by 28 publications

References 37 publications

Dual role of RACK1 in airway epithelial mesenchymal transition and apoptosis

Dual role of RACK1 in airway epithelial mesenchymal transition and apoptosis

2-BFI Provides Neuroprotection Against Inflammation and Necroptosis in a Rat Model of Traumatic Brain Injury

Tetrandrine alleviates inflammation and neuron apoptosis in experimental traumatic brain injury by regulating the IRE1α/JNK/CHOP signal pathway

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