Cellular Contractility Profiles of Human Diabetic Corneal Stromal Cells

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dc.creatorLam, Thi N.
dc.creatorNicholas, S. E.
dc.creatorChoi, Alexander
dc.creatorMa, Jian-Xing
dc.creatorKaramichos, Dimitrios
dc.creator.orcid0000-0002-8761-3824 (Karamichos, Dimitrios)
dc.date.accessioned2022-09-20T20:19:46Z
dc.date.available2022-09-20T20:19:46Z
dc.date.issued2021-06-04
dc.description.abstractDiabetic keratopathy is a corneal complication of diabetes mellitus (DM). Patients with diabetic keratopathy are prone to developing corneal haze, scarring, recurrent erosions, and significant wound healing defects/delays. The purpose of this study was to determine the contractility profiles in the diabetic human corneal stromal cells and characterize their molecular signatures. Primary human corneal fibroblasts from healthy, Type 1 DM (T1DM), and Type 2 DM (T2DM) donors were cultured using an established 3D collagen gel model. We tracked, measured, and quantified the contractile footprint over 9 days and quantified the modulation of specific corneal/diabetes markers in the conditional media and cell lysates using western blot analysis. Human corneal fibroblasts (HCFs) exhibited delayed and decreased contractility compared to that from T1DMs and T2DMs. Compared to HCFs, T2DMs demonstrated an initial downregulation of collagen I (day 3), followed by a significant upregulation by day 9. Collagen V was significantly upregulated in both T1DMs and T2DMs based on basal secretion, when compared to HCFs. Cell lysates were upregulated in the myofibroblast-associated marker, alpha-smooth muscle actin, in T2DMs on day 9, corresponding to the significant increase in contractility rate observed at the same time point. Furthermore, our data demonstrated a significant upregulation in IGF-1 expression in T2DMs, when compared to HCFs and T1DMs, at day 9. T1DMs demonstrated significant downregulation of IGF-1 expression, when compared to HCFs. Overall, both T1DMs and T2DMs exhibited increased contractility associated with fibrotic phenotypes. These findings, and future studies, may contribute to better understanding of the pathobiology of diabetic keratopathy and ultimately the development of new therapeutic approaches.
dc.description.sponsorshipThis study was supported by the National Eye Institute grant (EY028949).
dc.identifier.citationLam, T. N., Nicholas, S. E., Choi, A., Ma, J. X., & Karamichos, D. (2021). Cellular Contractility Profiles of Human Diabetic Corneal Stromal Cells. Analytical cellular pathology (Amsterdam), 2021, 9913210. https://doi.org/10.1155/2021/9913210
dc.identifier.issn2210-7185
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31788
dc.identifier.volume2021
dc.publisherHindawi
dc.relation.urihttps://doi.org/10.1155/2021/9913210
dc.rights.holderCopyright © 2021 Thi N. Lam et al.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceAnalytical Cellular Pathology
dc.subject.meshCell Culture Techniques, Three Dimensional / methods
dc.subject.meshCell Shape / physiology
dc.subject.meshCells, Cultured
dc.subject.meshCollagen Type I / metabolism
dc.subject.meshCollagen Type III / metabolism
dc.subject.meshCollagen Type V / metabolism
dc.subject.meshCorneal Diseases / etiology
dc.subject.meshCorneal Diseases / metabolism
dc.subject.meshCorneal Diseases / pathology
dc.subject.meshCorneal Stroma / cytology
dc.subject.meshCorneal Stroma / metabolism
dc.subject.meshDiabetes Mellitus, Type 1 / complications
dc.subject.meshDiabetes Mellitus, Type 2 / complications
dc.subject.meshFibroblasts / cytology
dc.subject.meshFibroblasts / metabolism
dc.subject.meshHumans
dc.subject.meshInsulin-Like Growth Factor I / metabolism
dc.subject.meshMiddle Aged
dc.subject.meshReceptor, IGF Type 1 / metabolism
dc.subject.meshStromal Cells / cytology
dc.subject.meshStromal Cells / metabolism
dc.subject.meshTime Factors
dc.titleCellular Contractility Profiles of Human Diabetic Corneal Stromal Cells
dc.typeArticle
dc.type.materialtext

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