Lack of Elevated Expression of TGFβ3 Contributes to the Delay of Epithelial Wound Healing in Diabetic Corneas DOI Creative Commons
Nan Gao, Fu‐Shin X. Yu

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(3), P. 35 - 35

Published: March 28, 2024

Purpose: To investigate the mechanisms underlying differential roles of TGFβ1 and TGFβ3 in accelerating corneal epithelial wound healing (CEWH) diabetic (DM) corneas, with normoglycemia (NL) corneas as control. Methods: Two types mice, human organ cultures, mouse progenitor cell lines, bone marrow–derived macrophages (BMDMs) were employed to assess effects on CEWH, utilizing quantitative PCR, western blotting, ELISA, whole-mount confocal microscopy. Results: Epithelial debridement led an increased expression cultured NL but only DM corneas. inhibition was significantly impeded, exogenous and, more potently, promoted CEWH TKE2 cells C57BL6 Wounding induced similar levels p-SMAD2/SMAD3 weaker ERK1/2, Akt, EGFR phosphorylation compared Whereas augmented SMAD2/SMAD3 phosphorylation, preferentially activated ERK, PI3K, Furthermore, differentially regulated S100a9, PAI-1, uPA/tPA, CCL3 Finally, M1 macrophage markers iNOS, CD86, CTGF, whereas M2 CD206 NGF BMDMs from db/db or db/+ mice. Conclusions: Hyperglycemia disrupts balanced TGFβ3/TGFβ1, resulting delayed including impaired sensory nerve regeneration cornea. Supplementing wounds may hold therapeutic potential for patients.

Language: Английский

Sensory Nerve Maintains Intervertebral Disc Extracellular Matrix Homeostasis Via CGRP/CHSY1 Axis DOI
Bo Hu, Xiao Lv,

Leixin Wei

et al.

Advanced Science, Journal Year: 2022, Volume and Issue: 9(30)

Published: Sept. 1, 2022

Abstract Sensory nerves are long being recognized as collecting units of various outer stimuli; recent advances indicate that the sensory nerve also plays pivotal roles in maintaining organ homeostasis. Here, this study shows orchestrates intervertebral disc (IVD) homeostasis by regulating its extracellular matrix (ECM) metabolism. Specifically, genetical denervation IVD results loss water preserve molecule chondroitin sulfate (CS), reduction CS bio‐synthesis gene synthase 1 (CHSY1) expression, and dysregulated ECM IVD. Particularly, knockdown neuros calcitonin gene‐related peptide (CGRP) expression induces similar metabolic disorder compared to model, effect is abolished CHSY1 knockout mice. Furthermore, vitro evidence CGRP regulates nucleus pulposus cell synthesis via receptor component activity‐modifying protein (RAMP1) cyclic AMP response element‐binding (CREB) signaling. Therapeutically, local injection forskolin significantly attenuates degeneration progression mouse annulus fibrosus puncture model. Overall, these maintains CGRP/CHSY1 axis promotes repair, expands understanding concerning how links system, thus shedding light on future development novel therapeutical strategy degeneration.

Language: Английский

Citations

24
Corneal dendritic cells in diabetes mellitus: A narrative review DOI Creative Commons
Fengyi Liu, Chang Liu,

Isabelle Xin Yu Lee

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 27, 2023

Diabetes mellitus is a global public health problem with both macrovascular and microvascular complications, such as diabetic corneal neuropathy (DCN). Using in-vivo confocal microscopy, nerve changes in DCN patients can be examined. Additionally, the morphology quantity of dendritic cells (DCs) corneas have also been observed. DCs are bone marrow-derived antigen-presenting that serve immunological non-immunological roles human corneas. However, role pathogenesis DC not well understood. In this article, we provide comprehensive review animal clinical studies report DCs, including density, maturation stages, relationships between nerves, epithelium, We discussed associations various or imaging parameters, age, status, blood metabolic parameters. Such information would valuable insight into development diagnostic, preventive, therapeutic strategies for DM-associated ocular surface complications.

Language: Английский

Citations

16
Interference of sympathetic overactivation restores limbal stem/progenitor cells function and accelerates corneal epithelial wound healing in diabetic mice DOI Open Access
Zhenzhen Zhang, Lingling Yang, Ya Li

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 161, P. 114523 - 114523

Published: March 15, 2023

Diabetic keratopathy (DK), the diabetic complication in cornea, is characterized by delayed epithelial regeneration and sensory nerve degeneration. The involvement of limbal stem/progenitor cells (LSPCs) dysfunction has been reported, however pathogenic mechanisms remain unclear. Here, we confirmed LSPCs mouse human corneas. sympathetic cornea was adjacent to LSPCs, overactivation found mice. Surgical pharmacological ablation nerves rescued function promoted corneal In contrast, both topical norepinephrine (NE) application chemogenetic directly impaired stemness proliferation characteristics as well normal regeneration. Moreover, identified that β2-adrenoceptor (Adrb2) predominant adrenergic receptor expressed single-cell sequencing real time PCR (RT-PCR) analysis sorted LSPCs. Adrb2 knockout mice exhibited enhancement function, compared with wild-type Similarly, specific antagonist ICI 118, 551 effectively accelerated restored function. Mechanistically, sonic hedgehog (Shh) activity mediated downstream effects NE-Adrb2 signaling pathway regulating Taken together, our data revealed impairment through NE-Adrb2-Shh pathway. interference may provide novel treatment strategies for keratopathy.

Language: Английский

Citations

15
Immune Fingerprint in Diabetes: Ocular Surface and Retinal Inflammation DOI Open Access
Madania Amorim, Beatriz Martins, Rosa Fernandes

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 9821 - 9821

Published: June 6, 2023

Diabetes is a prevalent global health issue associated with significant morbidity and mortality. Diabetic retinopathy (DR) well-known inflammatory, neurovascular complication of diabetes leading cause preventable blindness in developed countries among working-age adults. However, the ocular surface components diabetic eyes are also at risk damage due to uncontrolled diabetes, which often overlooked. Inflammatory changes corneas patients indicate that inflammation plays role complications, much like DR. The eye’s immune privilege restricts inflammatory responses, cornea retina have complex network innate cells maintain homeostasis. Nevertheless, low-grade contributes dysregulation. This article aims provide an overview discussion how affects system’s main components, immune-competent cells, mediators. By understanding these effects, potential interventions treatments may be improve patients.

Language: Английский

Citations

14
Lack of Elevated Expression of TGFβ3 Contributes to the Delay of Epithelial Wound Healing in Diabetic Corneas DOI Creative Commons
Nan Gao, Fu‐Shin X. Yu

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(3), P. 35 - 35

Published: March 28, 2024

Purpose: To investigate the mechanisms underlying differential roles of TGFβ1 and TGFβ3 in accelerating corneal epithelial wound healing (CEWH) diabetic (DM) corneas, with normoglycemia (NL) corneas as control. Methods: Two types mice, human organ cultures, mouse progenitor cell lines, bone marrow–derived macrophages (BMDMs) were employed to assess effects on CEWH, utilizing quantitative PCR, western blotting, ELISA, whole-mount confocal microscopy. Results: Epithelial debridement led an increased expression cultured NL but only DM corneas. inhibition was significantly impeded, exogenous and, more potently, promoted CEWH TKE2 cells C57BL6 Wounding induced similar levels p-SMAD2/SMAD3 weaker ERK1/2, Akt, EGFR phosphorylation compared Whereas augmented SMAD2/SMAD3 phosphorylation, preferentially activated ERK, PI3K, Furthermore, differentially regulated S100a9, PAI-1, uPA/tPA, CCL3 Finally, M1 macrophage markers iNOS, CD86, CTGF, whereas M2 CD206 NGF BMDMs from db/db or db/+ mice. Conclusions: Hyperglycemia disrupts balanced TGFβ3/TGFβ1, resulting delayed including impaired sensory nerve regeneration cornea. Supplementing wounds may hold therapeutic potential for patients.

Language: Английский

Citations

5