scholarly journals Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuan Zhang ◽  
Shengqian Dou ◽  
Xia Qi ◽  
Zhenzhen Zhang ◽  
Yujie Qiao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Network Analysis ◽  
Nerve Regeneration ◽  
Corneal Epithelial ◽  
Beneficial Effects ◽  
Epithelial Regeneration ◽  
Epithelial Wound Healing ◽  
Direct Target Gene ◽  
Inflammatory Processes

Diabetes mellitus (DM) is a complex metabolic disorder. Long-term hyperglycemia may induce diabetic keratopathy (DK), which is mainly characterized by delayed corneal epithelial regeneration. MicroRNAs (miRNAs) have been reported to play regulatory roles during tissue regeneration. However, the molecular mechanism by which miRNAs influence epithelial regeneration in DK is largely unknown. In this study, we performed miRNA and mRNA sequencing of regenerative corneal epithelium tissue from streptozotocin-induced type 1 diabetic (T1DM) and wild-type mice to screen for differentially expressed miRNAs and mRNAs. Based on regulatory network analysis, miR-223-5p was selected for subsequent experiments and Hpgds was then identified as a direct target gene. MiR-223-5p downregulation significantly promoted diabetic corneal epithelial wound healing and nerve regeneration. However, the beneficial effects of miR-223-5p inhibition were abolished by an Hpgds inhibitor. Furthermore, mechanistic studies demonstrated that miR-223-5p suppression ameliorated inflammation and enhanced cell proliferation signaling in DK. Taken together, our findings revealed that the regulatory role of miR-223-5p in diabetic corneal epithelial and nerve regeneration by mediating inflammatory processes and cell proliferation signaling. And silencing miR-223-5p may contribute to the development of potential therapeutic strategies for DK.

Role of the C Domain of IGFs in Synergistic Promotion, with a Substance P–Derived Peptide, of Rabbit Corneal Epithelial Wound Healing

2004 ◽  
Vol 45 (4) ◽  
pp. 1125 ◽  
Author(s):  
Naoyuki Yamada ◽  
Ryoji Yanai ◽  
Masatsugu Nakamura ◽  
Makoto Inui ◽  
Teruo Nishida
Keyword(s):  
Wound Healing ◽  
Substance P ◽  
Corneal Epithelial ◽  
Epithelial Wound Healing

scholarly journals MANF Promotes Diabetic Corneal Epithelial Wound Healing and Nerve Regeneration by Attenuating Hyperglycaemia-Induced Endoplasmic Reticulum Stress

2020 ◽  
Author(s):  
Ada Admin ◽  
Xiaochuan Wang ◽  
Weina Li ◽  
Qingjun Zhou ◽  
Jing Li ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Nerve Regeneration ◽  
Neurotrophic Factor ◽  
Therapeutic Modality ◽  
Subconjunctival Injection ◽  
Protective Effects ◽  
Corneal Epithelial ◽  
Epithelial Wound Healing

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.

scholarly journals Role of metaplasia during gastric regeneration

2020 ◽  
Vol 319 (6) ◽  
pp. C947-C954
Author(s):  
Emma Teal ◽  
Martha Dua-Awereh ◽  
Sabrina T. Hirshorn ◽  
Yana Zavros
Keyword(s):  
Cell Proliferation ◽  
Glutamate Transporter ◽  
Cell Loss ◽  
Redox Balance ◽  
Gastric Epithelium ◽  
Gastric Injury ◽  
M2 Macrophage ◽  
Cd44 Variant ◽  
Epithelial Regeneration

Spasmolytic polypeptide/trefoil factor 2 (TFF2)-expressing metaplasia (SPEM) is a mucous-secreting reparative lineage that emerges at the ulcer margin in response to gastric injury. Under conditions of chronic inflammation with parietal cell loss, SPEM has been found to emerge and evolve into neoplasia. Cluster-of-differentiation gene 44 (CD44) is known to coordinate normal and metaplastic epithelial cell proliferation. In particular, CD44 variant isoform 9 (CD44v9) associates with the cystine-glutamate transporter xCT, stabilizes the protein, and provides defense against reactive oxygen species (ROS). xCT stabilization by CD44v9 leads to defense against ROS by cystine uptake, glutathione (GSH) synthesis, and maintenance of the redox balance within the intracellular environment. Furthermore, p38 signaling is a known downstream ROS target, leading to diminished cell proliferation and migration, two vital processes of gastric epithelial repair. CD44v9 emerges during repair of the gastric epithelium after injury, where it is coexpressed with other markers of SPEM. The regulatory mechanisms for the emergence of CD44v9 and the role of CD44v9 during the process of gastric epithelial regeneration are largely unknown. Inflammation and M2 macrophage infiltration have recently been demonstrated to play key roles in the induction of SPEM after injury. The following review proposes new insights into the functional role of metaplasia in the process of gastric regeneration in response to ulceration. Our insights are extrapolated from documented studies reporting oxyntic atrophy and SPEM development and our current unpublished findings using the acetic acid-induced gastric injury model.

scholarly journals Rho kinases regulate corneal epithelial wound healing

2008 ◽  
Vol 295 (2) ◽  
pp. C378-C387 ◽  
Author(s):  
Jia Yin ◽  
Fu-Shin X. Yu
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Cell Migration ◽  
Rho Gtpase ◽  
Adhesion Formation ◽  
Small Gtpase ◽  
Corneal Epithelial Cell ◽  
Corneal Epithelial ◽  
Epithelial Wound Healing ◽  
Rho Kinases

We have previously shown that Rho small GTPase is required for modulating both cell migration and proliferation through cytoskeleton reorganization and focal adhesion formation in response to wounding. In the present study, we investigated the role of Rho kinases (ROCKs), major effectors of Rho GTPase, in mediating corneal epithelial wound healing. Both ROCK 1 and 2 were expressed and activated in THCE cells, an SV40-immortalized human corneal epithelial cell (HCEC) line, in response to wounding, lysophosphatidic acid, and heparin-binding EGF-like growth factor (HB-EGF) stimulations. The ROCK inhibitor Y-27632 efficiently antagonized ROCK activities without affecting Rho activation in wounded HCECs. Y-27632 promoted basal and HB-EGF-enhanced scratch wound healing and enhanced cell migration and adhesion to matrices, while retarded HB-EGF induced cell proliferation. E-cadherin- and β-catenin-mediated cell-cell junction and actin cytoskeleton organization were disrupted by Y-27632. Y-27632 impaired the formation and maintenance of tight junction barriers indicated by decreased trans-epithelial resistance and disrupted occludin staining. We conclude that ROCK activities enhance cell proliferation, promote epithelial differentiation, but negatively modulate cell migration and cell adhesion and therefore play a role in regulating corneal epithelial wound healing.

scholarly journals Role of VIP and Sonic Hedgehog signaling pathways in mediating epithelial wound healing, sensory nerve regeneration and their defects in diabetic corneas

2020 ◽  
Author(s):  
Ada Admin ◽  
Yangyang Zhang ◽  
Nan Gao ◽  
Lin Wu ◽  
Patrick S. Y. Lee ◽  
...  
Keyword(s):  
Wound Healing ◽  
Nerve Regeneration ◽  
Sonic Hedgehog ◽  
Sensory Nerve ◽  
Dependent Manner ◽  
Corneal Wound Healing ◽  
Epithelial Wound Healing ◽  
Corneal Wound ◽  
Diabetic Keratopathy

Diabetic Keratopathy, a sight-threatening corneal disease, comprises several symptomatic conditions including delayed epithelial wound healing, recurrent erosions, and sensory nerve (SN) neuropathy. We investigated the role of neuropeptides in mediating corneal wound healing, including epithelial wound closure and SN regeneration. Denervation by Resiniferatoxin severely impaired corneal wound healing and markedly up-regulated pro-inflammatory gene expression. Exogenous neuropeptides CGRP, SP, and VIP partially reversed Resiniferatoxin’s effects, with VIP specifically inducing IL-10 expression. Hence, we focused on VIP and observed that wounding induced VIP and VIPR1 expression in normal (NL), but not diabetic (DM) mouse corneas. Targeting VIPR1 in <em>NL</em> corneas attenuated corneal wound healing, dampened wound-induced expression of neurotrophic factors, and exacerbated inflammatory responses while exogenous VIP had the opposite effects in DM corneas. Remarkably, wounding and diabetes also affected the expression of Sonic Hedgehog (SHH) in a VIP-dependent manner. Downregulating SHH expression in NL corneas decreased, while exogenous SHH in DM corneas increased the rates of corneal wound healing. Furthermore, inhibition of SHH signaling dampened VIP-promoted corneal wound healing. We conclude that VIP regulates epithelial wound he<a></a><a>aling, inflammatory response, and nerve regeneration in the corneas in a</a> SHH-dependent manner, suggesting a therapeutic potential for these molecules in treating diabetic keratopathy.

Functional Role of PPARδ in Corneal Epithelial Wound Healing

2012 ◽  
Vol 180 (2) ◽  
pp. 583-598 ◽  
Author(s):  
Yoshikuni Nakamura ◽  
Takahiro Nakamura ◽  
Takeshi Tarui ◽  
Jun Inoue ◽  
Shigeru Kinoshita
Keyword(s):  
Wound Healing ◽  
Functional Role ◽  
Corneal Epithelial ◽  
Epithelial Wound Healing
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