Genistein‐Calcitriol Mitigates Hyperosmotic Stress‐Induced TonEBP, CFTR Dysfunction, VDR Degradation and Inflammation in Dry Eye Disease
Dry eye disease (DED) signs and symptoms are causally associated with increased ocular surface (OS) inflammation. Modulation of key regulators of aberrant OS inflammation is of interest for clinical management. We investigated the status and the potential to harness key endogenous protective factors...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.12858 |
| _version_ | 1818615761764089856 |
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| author | Trailokyanath Panigrahi Sharon D’Souza Rohit Shetty Archana Padmanabhan Nair Anuprita Ghosh Everette Jacob Remington Nelson Arkasubhra Ghosh Swaminathan Sethu |
| author_facet | Trailokyanath Panigrahi Sharon D’Souza Rohit Shetty Archana Padmanabhan Nair Anuprita Ghosh Everette Jacob Remington Nelson Arkasubhra Ghosh Swaminathan Sethu |
| author_sort | Trailokyanath Panigrahi |
| collection | DOAJ |
| description | Dry eye disease (DED) signs and symptoms are causally associated with increased ocular surface (OS) inflammation. Modulation of key regulators of aberrant OS inflammation is of interest for clinical management. We investigated the status and the potential to harness key endogenous protective factors, such as cystic fibrosis transmembrane conductance regulator (CFTR) and vitamin D receptor (VDR) in hyperosmotic stress‐associated inflammation in patients with DED and in vitro. Conjunctival impression cytology samples from control subjects (n = 11) and patients with DED (n = 15) were used to determine the status of hyperosmotic stress (TonEBP/NFAT5), inflammation (IL‐6, IL‐8, IL‐17A/F, TNFα, MMP9, and MCP1), VDR, and intracellular chloride ion (GLRX5) by quantitative polymerase chain reaction and/or immunofluorescence. Human corneal epithelial cells (HCECs) were used to study the effect of CFTR activator (genistein) and vitamin D (calcitriol) in hyperosmotic stress (HOs)‐induced response in vitro. Western blotting was used to determine the expression of these proteins, along with p‐p38. Significantly, higher expression of inflammatory factors, TonEBP, GLRX5, and reduced VDR were observed in patients with DED and in HOs‐induced HCECs in vitro. Expression of TonEBP positively correlated with expression of inflammatory genes in DED. Increased TonEBP and GLRX5 provides confirmation of osmotic stress and chloride ion imbalance in OS epithelium in DED. These along with reduced VDR suggests dysregulated OS homeostasis in DED. Combination of genistein and calcitriol reduced HOs‐induced TonEBP, inflammatory gene expression, and p‐p38, and abated VDR degradation in HCECs. Henceforth, this combination should be further explored for its relevance in the management of DED. |
| first_indexed | 2024-12-16T16:39:03Z |
| format | Article |
| id | doaj.art-6b175bf691644d6da18595b1e50c63c9 |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-12-16T16:39:03Z |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-6b175bf691644d6da18595b1e50c63c92022-12-21T22:24:22ZengWileyClinical and Translational Science1752-80541752-80622021-01-0114128829810.1111/cts.12858Genistein‐Calcitriol Mitigates Hyperosmotic Stress‐Induced TonEBP, CFTR Dysfunction, VDR Degradation and Inflammation in Dry Eye DiseaseTrailokyanath Panigrahi0Sharon D’Souza1Rohit Shetty2Archana Padmanabhan Nair3Anuprita Ghosh4Everette Jacob Remington Nelson5Arkasubhra Ghosh6Swaminathan Sethu7GROW Research Laboratory Narayana Nethralaya Foundation Bangalore IndiaDepartment of Cornea and Refractive Surgery Narayana Nethralaya Bangalore IndiaDepartment of Cornea and Refractive Surgery Narayana Nethralaya Bangalore IndiaGROW Research Laboratory Narayana Nethralaya Foundation Bangalore IndiaGROW Research Laboratory Narayana Nethralaya Foundation Bangalore IndiaGene Therapy Laboratory Department of Integrative Biology School of Bio Sciences and Technology Vellore Institute of Technology Vellore Tamil Nadu IndiaGROW Research Laboratory Narayana Nethralaya Foundation Bangalore IndiaGROW Research Laboratory Narayana Nethralaya Foundation Bangalore IndiaDry eye disease (DED) signs and symptoms are causally associated with increased ocular surface (OS) inflammation. Modulation of key regulators of aberrant OS inflammation is of interest for clinical management. We investigated the status and the potential to harness key endogenous protective factors, such as cystic fibrosis transmembrane conductance regulator (CFTR) and vitamin D receptor (VDR) in hyperosmotic stress‐associated inflammation in patients with DED and in vitro. Conjunctival impression cytology samples from control subjects (n = 11) and patients with DED (n = 15) were used to determine the status of hyperosmotic stress (TonEBP/NFAT5), inflammation (IL‐6, IL‐8, IL‐17A/F, TNFα, MMP9, and MCP1), VDR, and intracellular chloride ion (GLRX5) by quantitative polymerase chain reaction and/or immunofluorescence. Human corneal epithelial cells (HCECs) were used to study the effect of CFTR activator (genistein) and vitamin D (calcitriol) in hyperosmotic stress (HOs)‐induced response in vitro. Western blotting was used to determine the expression of these proteins, along with p‐p38. Significantly, higher expression of inflammatory factors, TonEBP, GLRX5, and reduced VDR were observed in patients with DED and in HOs‐induced HCECs in vitro. Expression of TonEBP positively correlated with expression of inflammatory genes in DED. Increased TonEBP and GLRX5 provides confirmation of osmotic stress and chloride ion imbalance in OS epithelium in DED. These along with reduced VDR suggests dysregulated OS homeostasis in DED. Combination of genistein and calcitriol reduced HOs‐induced TonEBP, inflammatory gene expression, and p‐p38, and abated VDR degradation in HCECs. Henceforth, this combination should be further explored for its relevance in the management of DED.https://doi.org/10.1111/cts.12858 |
| spellingShingle | Trailokyanath Panigrahi Sharon D’Souza Rohit Shetty Archana Padmanabhan Nair Anuprita Ghosh Everette Jacob Remington Nelson Arkasubhra Ghosh Swaminathan Sethu Genistein‐Calcitriol Mitigates Hyperosmotic Stress‐Induced TonEBP, CFTR Dysfunction, VDR Degradation and Inflammation in Dry Eye Disease Clinical and Translational Science |
| title | Genistein‐Calcitriol Mitigates Hyperosmotic Stress‐Induced TonEBP, CFTR Dysfunction, VDR Degradation and Inflammation in Dry Eye Disease |
| title_full | Genistein‐Calcitriol Mitigates Hyperosmotic Stress‐Induced TonEBP, CFTR Dysfunction, VDR Degradation and Inflammation in Dry Eye Disease |
| title_fullStr | Genistein‐Calcitriol Mitigates Hyperosmotic Stress‐Induced TonEBP, CFTR Dysfunction, VDR Degradation and Inflammation in Dry Eye Disease |
| title_full_unstemmed | Genistein‐Calcitriol Mitigates Hyperosmotic Stress‐Induced TonEBP, CFTR Dysfunction, VDR Degradation and Inflammation in Dry Eye Disease |
| title_short | Genistein‐Calcitriol Mitigates Hyperosmotic Stress‐Induced TonEBP, CFTR Dysfunction, VDR Degradation and Inflammation in Dry Eye Disease |
| title_sort | genistein calcitriol mitigates hyperosmotic stress induced tonebp cftr dysfunction vdr degradation and inflammation in dry eye disease |
| url | https://doi.org/10.1111/cts.12858 |
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