Similarities in DSG1 and KRT3 Downregulation through Retinoic Acid Treatment and PAX6 Knockdown Related Expression Profiles: Does PAX6 Affect RA Signaling in Limbal Epithelial Cells?

Congenital PAX6-aniridia is a rare panocular disease resulting from limbal stem cell deficiency. In PAX6-aniridia, the downregulation of the retinol-metabolizing enzymes ADH7 (All-trans-retinol dehydrogenase 7) and ALDH1A1/A3 (Retinal dehydrogenase 1, Aldehyde dehydrogenase family 1 member A3) have...

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Autores principales:	Lorenz Latta, Igor Knebel, Constanze Bleil, Tanja Stachon, Priya Katiyar, Claire Zussy, Fabian Norbert Fries, Barbara Käsmann-Kellner, Berthold Seitz, Nóra Szentmáry
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	aniridia retinoic acid PAX6 limbal epithelial cells DSG1 ADH7 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/98091ffec24d4b528c7db8b9aecb24ee
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spelling	oai:doaj.org-article:98091ffec24d4b528c7db8b9aecb24ee2021-11-25T16:53:23ZSimilarities in DSG1 and KRT3 Downregulation through Retinoic Acid Treatment and PAX6 Knockdown Related Expression Profiles: Does PAX6 Affect RA Signaling in Limbal Epithelial Cells?10.3390/biom111116512218-273Xhttps://doaj.org/article/98091ffec24d4b528c7db8b9aecb24ee2021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1651https://doaj.org/toc/2218-273XCongenital PAX6-aniridia is a rare panocular disease resulting from limbal stem cell deficiency. In PAX6-aniridia, the downregulation of the retinol-metabolizing enzymes ADH7 (All-trans-retinol dehydrogenase 7) and ALDH1A1/A3 (Retinal dehydrogenase 1, Aldehyde dehydrogenase family 1 member A3) have been described in limbal epithelial cells (LECs) and conjunctival epithelial cells. The aim of this study was to identify the role of retinol derivates in the differentiation of human LEC and its potential impact on aniridia-associated keratopathy development. Human LEC were isolated from healthy donor corneas and were cultured with retinol, retinoic acid, or pan-retinoic acid receptor antagonist (AGN 193109) acting on RARα, β, γ (NR1B1, NR1B2 NR1B3) or were cultured with pan-retinoid X receptor antagonist (UVI 3003) acting on RXR α, β, γ (retinoid X receptor, NR2B1, NR2B2, BR2B3). Using qPCR, differentiation marker and retinoid-/fatty acid metabolism-related mRNA expression was analysed. DSG1 (Desmoglein 1), KRT3 (Keratin 3), and SPINK7 (Serine Peptidase Inhibitor Kazal Type 7) mRNA expression was downregulated when retinoid derivates were used. AGN 193109 treatment led to the upregulation of ADH7, KRT3, and DSG1 mRNA expression and to the downregulation of KRT12 (Keratin 12) and KRT19 (Keratin 19) mRNA expression. Retinol and all-trans retinoic acid affect some transcripts of corneal LEC in a similar way to what has been observed in the LEC of PAX6-aniridia patients with the altered expression of differentiation markers. An elevated concentration of retinol derivatives in LEC or an altered response to retinoids may contribute to this pattern. These initial findings help to explain ocular surface epithelia differentiation disorders in PAX6-aniridia and should be investigated in patient cells or in cell models in the future in more detail.Lorenz LattaIgor KnebelConstanze BleilTanja StachonPriya KatiyarClaire ZussyFabian Norbert FriesBarbara Käsmann-KellnerBerthold SeitzNóra SzentmáryMDPI AGarticleaniridiaretinoic acidPAX6limbal epithelial cellsDSG1ADH7MicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1651, p 1651 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aniridia retinoic acid PAX6 limbal epithelial cells DSG1 ADH7 Microbiology QR1-502
spellingShingle	aniridia retinoic acid PAX6 limbal epithelial cells DSG1 ADH7 Microbiology QR1-502 Lorenz Latta Igor Knebel Constanze Bleil Tanja Stachon Priya Katiyar Claire Zussy Fabian Norbert Fries Barbara Käsmann-Kellner Berthold Seitz Nóra Szentmáry Similarities in DSG1 and KRT3 Downregulation through Retinoic Acid Treatment and PAX6 Knockdown Related Expression Profiles: Does PAX6 Affect RA Signaling in Limbal Epithelial Cells?
description	Congenital PAX6-aniridia is a rare panocular disease resulting from limbal stem cell deficiency. In PAX6-aniridia, the downregulation of the retinol-metabolizing enzymes ADH7 (All-trans-retinol dehydrogenase 7) and ALDH1A1/A3 (Retinal dehydrogenase 1, Aldehyde dehydrogenase family 1 member A3) have been described in limbal epithelial cells (LECs) and conjunctival epithelial cells. The aim of this study was to identify the role of retinol derivates in the differentiation of human LEC and its potential impact on aniridia-associated keratopathy development. Human LEC were isolated from healthy donor corneas and were cultured with retinol, retinoic acid, or pan-retinoic acid receptor antagonist (AGN 193109) acting on RARα, β, γ (NR1B1, NR1B2 NR1B3) or were cultured with pan-retinoid X receptor antagonist (UVI 3003) acting on RXR α, β, γ (retinoid X receptor, NR2B1, NR2B2, BR2B3). Using qPCR, differentiation marker and retinoid-/fatty acid metabolism-related mRNA expression was analysed. DSG1 (Desmoglein 1), KRT3 (Keratin 3), and SPINK7 (Serine Peptidase Inhibitor Kazal Type 7) mRNA expression was downregulated when retinoid derivates were used. AGN 193109 treatment led to the upregulation of ADH7, KRT3, and DSG1 mRNA expression and to the downregulation of KRT12 (Keratin 12) and KRT19 (Keratin 19) mRNA expression. Retinol and all-trans retinoic acid affect some transcripts of corneal LEC in a similar way to what has been observed in the LEC of PAX6-aniridia patients with the altered expression of differentiation markers. An elevated concentration of retinol derivatives in LEC or an altered response to retinoids may contribute to this pattern. These initial findings help to explain ocular surface epithelia differentiation disorders in PAX6-aniridia and should be investigated in patient cells or in cell models in the future in more detail.
format	article
author	Lorenz Latta Igor Knebel Constanze Bleil Tanja Stachon Priya Katiyar Claire Zussy Fabian Norbert Fries Barbara Käsmann-Kellner Berthold Seitz Nóra Szentmáry
author_facet	Lorenz Latta Igor Knebel Constanze Bleil Tanja Stachon Priya Katiyar Claire Zussy Fabian Norbert Fries Barbara Käsmann-Kellner Berthold Seitz Nóra Szentmáry
author_sort	Lorenz Latta
title	Similarities in DSG1 and KRT3 Downregulation through Retinoic Acid Treatment and PAX6 Knockdown Related Expression Profiles: Does PAX6 Affect RA Signaling in Limbal Epithelial Cells?
title_short	Similarities in DSG1 and KRT3 Downregulation through Retinoic Acid Treatment and PAX6 Knockdown Related Expression Profiles: Does PAX6 Affect RA Signaling in Limbal Epithelial Cells?
title_full	Similarities in DSG1 and KRT3 Downregulation through Retinoic Acid Treatment and PAX6 Knockdown Related Expression Profiles: Does PAX6 Affect RA Signaling in Limbal Epithelial Cells?
title_fullStr	Similarities in DSG1 and KRT3 Downregulation through Retinoic Acid Treatment and PAX6 Knockdown Related Expression Profiles: Does PAX6 Affect RA Signaling in Limbal Epithelial Cells?
title_full_unstemmed	Similarities in DSG1 and KRT3 Downregulation through Retinoic Acid Treatment and PAX6 Knockdown Related Expression Profiles: Does PAX6 Affect RA Signaling in Limbal Epithelial Cells?
title_sort	similarities in dsg1 and krt3 downregulation through retinoic acid treatment and pax6 knockdown related expression profiles: does pax6 affect ra signaling in limbal epithelial cells?
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/98091ffec24d4b528c7db8b9aecb24ee
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Similarities in DSG1 and KRT3 Downregulation through Retinoic Acid Treatment and PAX6 Knockdown Related Expression Profiles: Does PAX6 Affect RA Signaling in Limbal Epithelial Cells?

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