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Acetylcholine decreases formation of myofibroblasts and excessive extracellular matrix production in an in vitro human corneal fibrosis model
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).ORCID iD: 0000-0002-8039-493X
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).ORCID iD: 0000-0002-7906-9152
2020 (English)In: Journal of Cellular and Molecular Medicine (Print), ISSN 1582-1838, E-ISSN 1582-4934, Vol. 24, no 8, p. 4850-4862Article in journal (Refereed) Published
Abstract [en]

Acetylcholine (ACh) has been reported to play various physiological roles, including wound healing in the cornea. Here, we study the role of ACh in the transition of corneal fibroblasts into myofibroblasts, and in consequence its role in the onset of fibrosis, in an in vitro human corneal fibrosis model. Primary human keratocytes were obtained from healthy corneas. Vitamin C (VitC) and transforming growth factor-β1 (TGF-β1) were used to induce fibrosis in corneal fibroblasts. qRT-PCR and ELISA analyses showed that gene expression and production of collagen I, collagen III, collagen V, lumican, fibronectin (FN) and alpha-smooth muscle actin (α-SMA) were reduced by ACh in quiescent keratocytes. ACh treatment furthermore decreased gene expression and production of collagen I, collagen III, collagen V, lumican, FN and α-SMA during the transition of corneal fibroblasts into myofibroblasts, after induction of fibrotic process. ACh inhibited corneal fibroblasts from developing contractile activity during the process of fibrosis, as assessed with collagen gel contraction assay. Moreover, the effect of ACh was dependent on activation of muscarinic ACh receptors. These results show that ACh has an anti-fibrotic effect in an in vitro human corneal fibrosis model, as it negatively affects the transition of corneal fibroblasts into myofibroblasts. Therefore, ACh might play a role in the onset of fibrosis in the corneal stroma.

Place, publisher, year, edition, pages
John Wiley & Sons, 2020. Vol. 24, no 8, p. 4850-4862
Keywords [en]
collagens, cornea, fibrotic markers, keratocytes, scarring
National Category
Ophthalmology
Identifiers
URN: urn:nbn:se:umu:diva-170515DOI: 10.1111/jcmm.15168ISI: 000527848000043PubMedID: 32176460Scopus ID: 2-s2.0-85081750271OAI: oai:DiVA.org:umu-170515DiVA, id: diva2:1429041
Available from: 2020-05-07 Created: 2020-05-07 Last updated: 2023-03-24Bibliographically approved

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Sloniecka, MartaDanielson, Patrik

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