CXCL12 has therapeutic value in facial nerve injury and promotes Schwann cells autophagy and migration via PI3K-AKT-mTOR signal pathway

Gao, Dedong; Tang, Tianchi; Zhu, Jin; Tang, Yinda; Sun, Hui; Li, Shiting

doi:10.1016/j.ijbiomac.2018.10.212

Cited by 46 publications

(40 citation statements)

References 26 publications

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“…In contrast, metformin has been found to enhance levels of autophagy and inhibit the migration of endothelial progenitor cells (Li W. D. et al, 2017). In a recent study, stromal cell-derived factor (SDF-1α or CXCL12) showed a pivotal role in regulating SC migration by enhancing autophagy after facial nerve injury (Gao et al, 2019). We found that EpoB induced autophagy in SCs, and that inhibition of autophagy by 3-MA was capable of inhibiting the EpoB-enhanced SC migration.…”

Section: Discussionmentioning

confidence: 66%

Epothilone B Facilitates Peripheral Nerve Regeneration by Promoting Autophagy and Migration in Schwann Cells

Zhou

Gao

et al. 2020

Front. Cell. Neurosci.

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The search for drugs that can facilitate axonal regeneration and elongation following peripheral nerve injury has been an area of increasing interest in recent years. Epothilone B (EpoB) is an FDA-approved antineoplastic agent, which shows the capacity to induce α-tubulin polymerization and to improve the stability of microtubules. Recently, it has been increasingly recognized that EpoB has a regenerative effect in the central nervous system. However, the information currently available regarding the potential therapeutic effect of EpoB on peripheral nerve regeneration is limited. Here, we used a rat sciatic crush injury model system to determine that EpoB strikingly improved axonal regeneration and recovery of function. Also, EpoB (1 nM) did not result in significant apoptosis in Schwann cells (SCs) and showed little effect on their viability either. Interestingly, EpoB (1 nM) significantly enhanced migration in SCs, which was inhibited by autophagy inhibitors 3-methyladenine (3-MA). Since PI3K/Akt signaling has been implicated in regulating autophagy, we further examined the involvement of PI3K/Akt in the process of EpoB-induced SC migration. We found that EpoB (1 nM) significantly inhibited phosphorylation of PI3K and Akt in SCs. Further studies showed that both EpoB-enhanced migration and autophagy were increased/inhibited by inhibition/activation of PI3K/Akt signaling with LY294002 or IGF-1. In conclusion, EpoB can promote axonal regeneration following peripheral nerve injury by enhancing the migration of SCs, with this activity being controlled by PI3K/Akt signaling-mediated autophagy in SCs. This underscores the potential therapeutic value of EpoB in enhancing regeneration and functional recovery in cases of peripheral nerve injury.

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Section: Discussionmentioning

confidence: 66%

Epothilone B Facilitates Peripheral Nerve Regeneration by Promoting Autophagy and Migration in Schwann Cells

Zhou

Gao

et al. 2020

Front. Cell. Neurosci.

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“…PI3K-AKT signaling was partially inactivated after CLCA4 over-expression in CRC cells which suggests that PI3K-AKT is actually one of the important signal transduction pathways mediating CLCA4 to play biological roles. To further illustrate this point, insulin growth factor-1 (IGF-1) was used to activate PI3K-AKT signaling in CLCA4 over-expressed CRC cells and then Transwell and scratch assays were performed again to assess the invasion and migration capacity of CLCA4 gain-of-function model cells [19,20]. The results demonstrated that the activation of PI3K-AKT signaling by IGF-1 treatment could significantly restore the inhibition of CLCA4 on the invasion (Figure 4A, 4B) and migration (Figure 4C, 4D) of CRC cells.…”

Section: Resultsmentioning

confidence: 99%

Calcium-Activated Chloride Channel A4 (CLCA4) Plays Inhibitory Roles in Invasion and Migration Through Suppressing Epithelial-Mesenchymal Transition via PI3K/AKT Signaling in Colorectal Cancer

et al. 2019

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Background Calcium-activated chloride channel A4 (CLCA4) is known as a tumor suppressor which contributes to the progression of a number of types of malignant tumors. However, little is known about the functional roles of CLCA4 in colorectal cancer (CRC). Material/Methods In this study, the expression patterns and dysregulation of mRNAs in CRC tissues were profiled by analyzing GSE21510 datasets from Gene Expression Omnibus database which contains 104 primary hepatocellular carcinoma tissues and 24 normal liver tissues, and by performing Kaplan-Meier analysis of TCGA data. Additionally, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) were performed using clinical tissues collected at our institute. In order to explore the functional role of CLCA4, gain-of-function cell models were constructed in SW620 and LoVo cells. Wound healing assay and Transwell assay were carried out to access the cell migration and invasion ability. Results It was found that CLCA4 was an independent predictor for overall survival and lymph node metastasis. Additionally, immunohistochemistry and qRT-PCR results of the clinical tissues collected as part of our study further confirmed this correlation. In vitro experiments demonstrated that over-expression of CLCA4 could inhibit cell migration and invasion by suppressing epithelial-mesenchymal transition (EMT) via PI3K/ATK signaling and change the expression patterns of EMT markers in CLCA4-gain-of-function cell models. Conclusions CLCA4 inhibits migration and invasion by suppressing EMT via PI3K/ATK signaling and predicts favorable prognosis of CRC which may help to distinguish potential risk of lymph node metastasis in CRC.

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“…As described in our previous publication, 22 SCs were isolated from the sciatic nerves of SD rats at postnatal day 3. The nerve tissues were harvested and dissociated with 0.25% of trypsin-EDTA (Gibco) at 37°C for 30 minutes, and single cells suspended in DMEM/F12 (Hyclone) containing 10% FBS (Hyclone) were plated onto Poly-L-lysine-coated dishes.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway

et al. 2020

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Many factors are involved in the process of nerve regeneration. Understanding the mechanisms regarding how these factors promote an efficient remyelination is crucial to deciphering the molecular and cellular processes required to promote nerve repair. Schwann cells (SCs) play a central role in the process of peripheral nerve repair/regeneration. Using a model of facial nerve crush injury and repair, we identified Annexin A1 (ANXA1) as the extracellular trigger of SC proliferation and migration. ANXA1 activated formyl peptide receptor 2 (FPR2) receptors and the downstream adenosine 5′‐monophosphate (AMP)‐activated protein kinase (AMPK) signaling cascade, leading to SC proliferation and migration in vitro. SCs lacking FPR2 or AMPK displayed a defect in proliferation and migration. After facial nerve injury (FNI), ANXA1 promoted the proliferation of SCs and nerve regeneration in vivo. Collectively, these data identified the ANXA1/FPR2/AMPK axis as an important pathway in SC proliferation and migration. ANXA1‐induced remyelination and SC proliferation promotes FNI regeneration.

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CXCL12 has therapeutic value in facial nerve injury and promotes Schwann cells autophagy and migration via PI3K-AKT-mTOR signal pathway

Cited by 46 publications

References 26 publications

Epothilone B Facilitates Peripheral Nerve Regeneration by Promoting Autophagy and Migration in Schwann Cells

Epothilone B Facilitates Peripheral Nerve Regeneration by Promoting Autophagy and Migration in Schwann Cells

Calcium-Activated Chloride Channel A4 (CLCA4) Plays Inhibitory Roles in Invasion and Migration Through Suppressing Epithelial-Mesenchymal Transition via PI3K/AKT Signaling in Colorectal Cancer

ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway

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