FGF10 Enhances Peripheral Nerve Regeneration via the Preactivation of the PI3K/Akt Signaling-Mediated Antioxidant Response

Dong, Lvpeng; Li, Rui; Li, Duohui; Wang, Beini; Lu, Yingfeng; Li, Peifeng; Yu, Fangzheng; Jin, Yonglong; Xiao, Ni; Wu, Yanqing; Yang, Shengnan; Lv, Guanxi; Li, Xiaokun; Xiao, Jian; Wang, Jian

doi:10.3389/fphar.2019.01224

Cited by 38 publications

(45 citation statements)

References 62 publications

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“…FGF10 is a member of the FGF family with multifunctional effect in the regulation of development, wound healing, and tissue regeneration. It has been proved that FGF10 can ameliorate cerebral I/R injury and spinal cord injury via inhibiting NF-kB-dependent inflammation and activating the PI3K/Akt signaling pathway (Li et al, 2016;Chen et al, 2017;Dong et al, 2019). In our previous study, we demonstrated that FGF10 can protect the kidney against apoptosis via the regulation of inflammatory response and autophagy (Tan et al, 2018).…”

Section: Discussionmentioning

confidence: 95%

Fibroblast Growth Factor 10 Attenuates Renal Damage by Regulating Endoplasmic Reticulum Stress After Ischemia–Reperfusion Injury

et al. 2020

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Renal ischemia-reperfusion (I/R) injury is a predominant cause of acute kidney injury (AKI), the pathologic mechanism of which is highly complex involving reactive oxygen species (ROS) accumulation, inflammatory response, autophagy, apoptosis as well as endoplasmic reticulum (ER) stress. Fibroblast growth factor 10 (FGF10), as a multifunctional growth factor, plays crucial roles in embryonic development, adult homeostasis, and regenerative medicine. Herein, we investigated the molecular pathways underlying the protective effect of FGF10 on renal I/R injury using Sprague-Dawley rats. Results showed that administration of FGF10 not only effectively inhibited I/Rinduced activation of Caspase-3 and expression of Bax, but also alleviated I/R evoked expression of ER stress-related proteins in the kidney including CHOP, GRP78, XBP-1, and ATF-4 and ATF-6. The protective effect of FGF10 against apoptosis and ER stress was recapitulated by in vitro experiments using oxidative damaged NRK-52E cells induced by tert-Butyl hydroperoxide (TBHP). Significantly, U0126, a selective noncompetitive inhibitor of MAP kinase kinases (MKK), largely abolished the protective role of FGF10. Taken together, both in vivo and in vitro experiments indicated that FGF10 attenuates I/R-induced renal epithelial apoptosis by suppressing excessive ER stress, which is, at least partially, mediated by the activation of the MEK-ERK1/2 signaling pathway. Therefore, our present study revealed the therapeutic potential of FGF10 on renal I/R injury.

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Section: Discussionmentioning

confidence: 95%

Fibroblast Growth Factor 10 Attenuates Renal Damage by Regulating Endoplasmic Reticulum Stress After Ischemia–Reperfusion Injury

et al. 2020

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“…Similarly, these therapeutic effects were partially abolished when AST was combined with LY294002. This result might be explained that the nerve tissue had the capability of synthetizing and secreting some antioxidant enzymes to resist SCII-induced oxidative damage, although this capability did not satisfied the demand of cellular antioxidant defense [38]. After administration of AST to the SCII rats, the PI3K/Akt/GSK-3β signaling pathway associated with antioxidant stress was activated, which further enhanced antioxidative capability and then promoted nerve regeneration.…”

Section: Discussionmentioning

confidence: 96%

Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats

Fu¹,

Sun²,

Wei³

et al. 2020

J Orthop Surg Res

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Background: Ischemia-reperfusion injury of the spinal cord (SCII) often leads to unalterable neurological deficits, which may be associated with apoptosis induced by oxidative stress and inflammation. Astaxanthin (AST) is a strong antioxidant and anti-inflammatory agent with multitarget neuroprotective effects. This study aimed to investigate the potential therapeutic effects of AST for SCII and the molecular mechanism. Methods: Rat models of SCII with abdominal aortic occlusion for 40 min were carried out to investigate the effects of AST on the recovery of SCII. Tarlov's scores were used to assess the neuronal function; HE and TUNEL staining were used to observe the pathological morphology of lesions. Neuron oxidative stress and inflammation were measured using commercial detection kits. Flow cytometry was conducted to assess the mitochondrial swelling degree. Besides, Western blot assay was used to detect the expression of PI3K/Akt/GSK-3β pathway-related proteins, as well as NOX2 and NLRP3 proteins. Results: The results demonstrated that AST pretreatment promoted the hind limb motor function recovery and alleviated the pathological damage induced by SCII. Moreover, AST significantly enhanced the antioxidative stress response and attenuated mitochondrial swelling. However, AST pretreatment hardly inhibited the levels of proinflammatory cytokines after SCII. Most importantly, AST activated p-Akt and p-GSK-3β expression levels. Meanwhile, cotreatment with LY294002 (a PI3K inhibitor) was found to abolish the above protective effects observed with the AST pretreatment. Conclusion: Overall, these results suggest that AST pretreatment not only mitigates pathological tissue damage but also effectively improves neural functional recovery following SCII, primarily by alleviating oxidative stress but not inhibiting inflammation. A possible underlying molecular mechanism of AST may be mainly attributed to the activation of PI3K/Akt/GSK-3β pathway.

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“…Pik3r2 is a protein-coding gene that encodes the regulatory component of phosphoinositide 3-kinase (PI3K), which has a diverse range of cell functions including proliferation and survival. In peripheral nerve injury, the related PI3K/protein kinase B (Akt) pathway might be involved in the Schwann cell response to excessive oxidative stress-induced apoptosis [ 50 ]. Further validation regarding the pivotal role of the abovementioned regulating genes responsible for prolonged neuroinflammation is needed in the future.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Neuropathology after Nerve Release in Chronic Constriction Injury of Rat Sciatic Nerve

Chen

Lin

et al. 2021

IJMS

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Peripheral compressive neuropathy causes significant neuropathic pain, muscle weakness and prolong neuroinflammation. Surgical decompression remains the gold standard of treatment but the outcome is suboptimal with a high recurrence rate. From mechanical compression to chemical propagation of the local inflammatory signals, little is known about the distinct neuropathologic patterns and the genetic signatures after nerve decompression. In this study, controllable mechanical constriction forces over rat sciatic nerve induces irreversible sensorimotor dysfunction with sustained local neuroinflammation, even 4 weeks after nerve release. Significant gene upregulations are found in the dorsal root ganglia, regarding inflammatory, proapoptotic and neuropathic pain signals. Genetic profiling of neuroinflammation at the local injured nerve reveals persistent upregulation of multiple genes involving oxysterol metabolism, neuronal apoptosis, and proliferation after nerve release. Further validation of the independent roles of each signal pathway will contribute to molecular therapies for compressive neuropathy in the future.

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FGF10 Enhances Peripheral Nerve Regeneration via the Preactivation of the PI3K/Akt Signaling-Mediated Antioxidant Response

Cited by 38 publications

References 62 publications

Fibroblast Growth Factor 10 Attenuates Renal Damage by Regulating Endoplasmic Reticulum Stress After Ischemia–Reperfusion Injury

Fibroblast Growth Factor 10 Attenuates Renal Damage by Regulating Endoplasmic Reticulum Stress After Ischemia–Reperfusion Injury

Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats

Investigation of Neuropathology after Nerve Release in Chronic Constriction Injury of Rat Sciatic Nerve

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