Please use this identifier to cite or link to this item:
Full metadata record
DC FieldValueLanguage
dc.contributor.authorTan, Mark Wei Yien_US
dc.contributor.authorTan, Wei Renen_US
dc.contributor.authorKong, Ze Qingen_US
dc.contributor.authorToh, Jun Hongen_US
dc.contributor.authorWee, Jonathan Wei Kiaten_US
dc.contributor.authorTeo, Erica Mei Lingen_US
dc.contributor.authorCheng, Hong Shengen_US
dc.contributor.authorWang, Xiaomengen_US
dc.contributor.authorTan, Nguan Soonen_US
dc.identifier.citationTan, M. W. Y., Tan, W. R., Kong, Z. Q., Toh, J. H., Wee, J. W. K., Teo, E. M. L., Cheng, H. S., Wang, X. & Tan, N. S. (2021). High glucose restraint of acetylcholine-induced keratinocyte epithelial-mesenchymal transition is mitigated by p38 inhibition. Journal of Investigative Dermatology, 141(6), 1438-1449.
dc.description.abstractNon-neuronal acetylcholine (Ach) plays important roles in various aspects of cell biology and homeostasis outside the neural system. Keratinocytes (KCs) have a functional cholinergic mechanism, suggesting that they respond to Ach. However, the physiological role and mechanism by which Ach modulates wound KC behavior in both nondiabetic and diabetic conditions are unexplored. We found an enrichment in neurotransmitter-related pathways in microdissected-migrating nondiabetic and diabetic KCs. We showed that Ach upregulated TGFβRII through Src-extracellular signal‒regulated kinase 1/2 pathway to potentiate TGFβ1-mediated epithelial‒mesenchymal transition in normoglycemic condition. Unexpectedly, KCs were nonresponsive to the elevated endogenous Ach in a hyperglycemic environment. We further showed that the activation of p38 MAPK in high glucose condition interferes with Src-extracellular signal‒regulated kinase 1/2 signaling, resulting in Ach resistance that could be rescued by inhibiting p38 MAPK. A better understanding of the cholinergic physiology in diabetic KCs could improve wound management and care. The finding suggests that mitigating the inhibitory effect of diabetic wound microenvironment has a direct clinical implication on the efficacy and safety of various wound healing agents to improve chronic diabetic wounds.en_US
dc.description.sponsorshipMinistry of Education (MOE)en_US
dc.relationMOE2018-T2- 1-043en_US
dc.relation.ispartofJournal of Investigative Dermatologyen_US
dc.rights© 2021 The Authors. All rights reserved. This paper was published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology in Journal of Investigative Dermatology and is made available with permission of The Authors.en_US
dc.subjectScience::Biological sciencesen_US
dc.titleHigh glucose restraint of acetylcholine-induced keratinocyte epithelial-mesenchymal transition is mitigated by p38 inhibitionen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.contributor.schoolInterdisciplinary Graduate School (IGS)en_US
dc.contributor.organizationInstitute of Molecular and Cell Biology, A*STARen_US
dc.contributor.organizationSingapore Eye Research Instituteen_US
dc.contributor.researchNTU Institute for Health Technologiesen_US
dc.description.versionSubmitted/Accepted versionen_US
dc.subject.keywordsCell Functionen_US
dc.description.acknowledgementThis research is supported by the Singapore Ministry of Education under its Singapore Ministry of Education Academic Research Fund Tier 1 (2014-T1-002-138-03) and Tier 2 (MOE2018-T2- 1-043) to NST.en_US
item.fulltextWith Fulltext-
Appears in Collections:IGS Journal Articles
LKCMedicine Journal Articles
SBS Journal Articles
Files in This Item:
File Description SizeFormat 
High Glucose Restraint of Acetylcholine-Induced Keratinocyte Epithelial-Mesenchymal Transition Is Mitigated by p38 Inhibition.pdf
  Until 2022-07-07
6.24 MBAdobe PDFUnder embargo until Jul 07, 2022

Page view(s)

Updated on Jul 4, 2022

Google ScholarTM




Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.