Objective: Hcy is an independent risk factor for cerebrovascular disease and cognitive impairment. The purpose of this study was to elucidate the role of mGluR5 in Hcy-mediated impairment of cerebral endothelial wound repair.
Methods: Mouse CMVECs (bEnd.3) were used in conjunction with directed pharmacology and shRNA. AutoDock was used to simulate the docking of ligand-receptor interactions.
Results: Hcy (20 μM) significantly increased Cx43-pS368 by mGluR5- and PKC-dependent mechanisms. Hcy attenuated wound repair by an mGluR5-dependent mechanism over the six-day study period but did not alter cell proliferation in a proliferation assay, suggesting that the attenuation of wound repair may be due to dysfunctional migration in HHcy. Hcy increased the expression of Cx43 and Cx43-pS368 at the wound edge by activating mGluR5. Direct activation of mGluR5, using the specific agonist CHPG, was sufficient to reproduce the results whereas KO of mGluR5 with shRNA, or inhibition with MPEP, blocked the response to Hcy.
Conclusions: Inhibition of mGluR5 activation could be a novel strategy for promoting endothelial wound repair in patients with HHcy. Activation of mGluR5 may be a viable strategy for disrupting angiogenesis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359906 | PMC |
| http://dx.doi.org/10.1111/j.1549-8719.2012.00159.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Permanent defects in renal medullary structure and function after reversal of urinary obstruction.
JCI Insight
January 2025
Division of Nephrology, Department of Medicine, Vanderbildt University Medical Center, Nashville, United States of America.
Urinary obstruction causes injury to the renal medulla, impairing the ability to concentrate urine, and increasing the risk of progressive kidney disease. However, the regenerative capacity of the renal medulla after reversal of obstruction is poorly understood. To investigate this, we developed a mouse model of reversible urinary obstruction.
View Article and Find Full Text PDFRed and blue LED light increases the survival rate of random skin flaps in rats after MRSA infection.
Lasers Med Sci
January 2025
Department of Plastic and Reconstructive Surgery, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, Anhui Province, 230601, P.R. China.
Skin flap transplantation is a conventional wound repair method in plastic and reconstructive surgery, but infection and ischemia are common complications. Photobiomodulation (PBM) therapy has shown promise for various medical problems, including wound repair processes, due to its capability to accelerate angiogenesis and relieve inflammation. This study investigated the effect of red and blue light on the survival of random skin flaps in methicillin-resistant Staphylococcus aureus (MRSA)-infected Sprague Dawley (SD) rats.
View Article and Find Full Text PDFEndothelial FOXM1 and Dab2 promote diabetic wound healing.
JCI Insight
January 2025
Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA.
Diabetes mellitus can cause impaired and delayed wound healing, leading to lower extremity amputations; however, the mechanisms underlying the regulation of vascular endothelial growth factor-dependent (VEGF-dependent) angiogenesis remain unclear. In our study, the molecular underpinnings of endothelial dysfunction in diabetes are investigated, focusing on the roles of disabled-2 (Dab2) and Forkhead box M1 (FOXM1) in VEGF receptor 2 (VEGFR2) signaling and endothelial cell function. Bulk RNA-sequencing analysis identified significant downregulation of Dab2 in high-glucose-treated primary mouse skin endothelial cells.
View Article and Find Full Text PDFBioactive Glasses: Advancing Skin Tissue Repair through Multifunctional Mechanisms and Innovations.
Biomater Res
January 2025
Department of Burn and Plastic Surgery, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China.
As a complex and dynamically regulated process, wound healing is collaboratively carried out by multiple types of cells. However, the precise mechanisms by which these cells contribute to immune regulation are not yet fully understood. Although research on bone regeneration has been quite extensive, the application of bioactive glass (BG) in skin tissue repair remains still relatively underexplored.
View Article and Find Full Text PDFIn Vitro Assessment of Chitosan-PEG Hydrogels Enriched with MSCs-Exosomes for Enhancing Wound Healing.
Macromol Biosci
January 2025
Department of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3082/12, Brno, 61600, Czech Republic.
Regenerating skin tissue remains a major challenge in medical science, especially due to the risk of scarring and prolonged healing, which becomes even more complicated in people with diabetes. Recent advancements have led to the creation of therapeutic dressings incorporating drug-delivery systems to tackle these issues. Exosomes (Exos) derived from mesenchymal stem cells (MSCs) have gained significant attention for mediating therapy without directly using cells, thanks to their natural anti-inflammatory and tissue repair properties mirroring those of MSCs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!