scholarly journals AQP5 Facilitates Corneal Epithelial Wound Healing and Nerve Regeneration by Reactivating Akt Signaling Pathway

Author(s):  
Yaning Liu ◽  
Guohu Di ◽  
Yihui Wang ◽  
Daochen Chong ◽  
Xin Cao ◽  
...  
Author(s):  
Ada Admin ◽  
Xiaochuan Wang ◽  
Weina Li ◽  
Qingjun Zhou ◽  
Jing Li ◽  
...  

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic factor widely expressed in mammalian tissues and exerts critical protective effects on neurons and other cell types in various disease models, such as those for diabetes. However, to date, the expression and roles of MANF in the cornea, with or without diabetic keratopathy (DK), remain unclear. <a>Here, we demonstrated</a> that MANF is abundantly expressed in normal corneal epithelial cells, however, MANF expression was significantly reduced in both unwounded and wounded corneal epithelium in STZ-induced type 1 diabetic C57BL/6 mice. Recombinant MANF significantly promoted normal and diabetic corneal epithelial wound healing and nerve regeneration. Furthermore, MANF inhibited hyperglycaemia-induced endoplasmic reticulum (ER) stress and ER stress-mediated apoptosis. Attenuation of ER stress with 4-phenylbutyric acid (4-PBA) also ameliorated corneal epithelial closure and nerve regeneration. However, the beneficial effects of MANF and 4-PBA were abolished by an Akt inhibitor and Akt-specific siRNA. Finally, we revealed that the subconjunctival injection of MANF-specific siRNA prevented corneal epithelial wound healing and nerve regeneration. Our results provide important evidence that hyperglycaemia-suppressed MANF expression may contribute to delayed corneal epithelial wound healing and impaired nerve regeneration by increasing ER stress, and MANF may be a useful therapeutic modality for treating DK.


2020 ◽  
Vol 9 (3) ◽  
pp. 5
Author(s):  
Jing Li ◽  
Xia Qi ◽  
Xiaochuan Wang ◽  
Weina Li ◽  
Ya Li ◽  
...  

Diabetes ◽  
2020 ◽  
Vol 69 (6) ◽  
pp. 1264-1278 ◽  
Author(s):  
Xiaochuan Wang ◽  
Weina Li ◽  
Qingjun Zhou ◽  
Jing Li ◽  
Xiaolei Wang ◽  
...  

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Zhongping Jiang ◽  
Jie Wei ◽  
Weize Yang ◽  
Wen Li ◽  
Feng Liu ◽  
...  

Abstract Background: Keratinocyte migration is essential for skin wound healing and recent studies demonstrated that microRNAs (miRNAs) are involved in the differentiation, migration and apoptosis in keratinocytes. However, the function of miR-26a in wound healing remains to be largely explored. Methods: Northern blot and quantitative reverse transcriptase PCR (qRT-PCR) were used to detect the miR-26a expression and Western blot was used to detect integrin α-5 (ITGA5), phosphatidylinositol-3-kinase (PI3K), p-PI3K, protein kinase B (AKT) and p-AKT protein expression in immortalized human keratinocyte cell line HaCaT and normal human epidermal keratinocytes (NHEK) after 2 ng/ml transforming growth factor-β1 (TGF-β1) treatment for 0, 6, 12 and 24 h. Transwell assay and Wound healing assay were introduced to measure the cell migration of HaCaT cells. TargetScan online database, luciferase reporter assay and RNA immunoprecipitation (RIP) were employed to confirm the relationship between miR-26a and ITGA5. Results: The RNA expression of miR-26a was down-regulated and ITGA5 protein expression was up-regulated by TGF-β1 treatment in HaCaT and NHEK cells in a time-dependent manner. MiR-26a overexpression inhibited the migration of HaCaT cells induced by TGF-β1 while miR-26a inhibitor enhanced the migration. ITGA5 was a downstream target mRNA and regulated by miR-26a. ITGA5 overexpression reversed the inhibitory effect of miR-26a on migration in HaCaT, while ITGA5 knockdown attenuated the stimulative effect of miR-26a inhibitor in HaCaT via PI3K/AKT signaling pathway. Conclusion: MiR-26a overexpression inhibited TGF-β1 induced HaCaT cells migration via down-regulating ITGA5 through activating the PI3K/AKT signaling pathway.


2018 ◽  
Vol 370 (2) ◽  
pp. 333-342 ◽  
Author(s):  
Wei Zhang ◽  
Xiaozhi Bai ◽  
Bin Zhao ◽  
Yan Li ◽  
Yijie Zhang ◽  
...  

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