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Stanniocalcin2, but Not Stanniocalcin1, Responds to Hypoxia in a HIF1-Dependent Manner in the Retina

The quest for neuroprotective factors that can prevent or slow down the progression of retinal degeneration is still ongoing. Acute hypoxic stress has been shown to provide transient protection against subsequent damage in the retina. Stanniocalcins – STC1 and STC2 – are secreted glycoproteins that...

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Autores principales: Ail, Divya, Samardzija, Marijana, Chang, Andy C. M., Keck, Jadwiga, Reddel, Roger R., Grimm, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259883/
https://www.ncbi.nlm.nih.gov/pubmed/35812222
http://dx.doi.org/10.3389/fnins.2022.882559
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author Ail, Divya
Samardzija, Marijana
Chang, Andy C. M.
Keck, Jadwiga
Reddel, Roger R.
Grimm, Christian
author_facet Ail, Divya
Samardzija, Marijana
Chang, Andy C. M.
Keck, Jadwiga
Reddel, Roger R.
Grimm, Christian
author_sort Ail, Divya
collection PubMed
description The quest for neuroprotective factors that can prevent or slow down the progression of retinal degeneration is still ongoing. Acute hypoxic stress has been shown to provide transient protection against subsequent damage in the retina. Stanniocalcins – STC1 and STC2 – are secreted glycoproteins that are hypoxia-regulated and were shown to be cytoprotective in various in vitro studies. Hence, we investigated the expression of stanniocalcins in the normal, degenerating and hypoxic retina. We show that the expression of Stc1 and Stc2 in the retina was detectable as early as postnatal day 10 and persisted during aging. Retinal expression of Stc2, but not Stc1, was induced in mice in an in vivo model of acute hypoxia and a genetic model of chronic hypoxia. Furthermore, we show that HIF1, not HIF2, is responsible for regulating Stc2 in cells with the molecular response to hypoxia activated due to the absence of von Hippel Lindau protein. Surprisingly, Stc2 was not normally expressed in photoreceptors but in the inner retina, as shown by laser capture microdissection and immunofluorescence data. The expression of both Stc1 and Stc2 remained unchanged in the degenerative retina with an almost complete loss of photoreceptors, confirming their expression in the inner retina. However, the absence of either Stc1 or Stc2 had no effect on retinal architecture, as was evident from retinal morphology of the respective knockout mice. Taken together our data provides evidence for the differential regulation of STC1 and STC2 in the retina and the prospect of investigating STC2 as a retinal neuroprotective factor.
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spelling pubmed-92598832022-07-08 Stanniocalcin2, but Not Stanniocalcin1, Responds to Hypoxia in a HIF1-Dependent Manner in the Retina Ail, Divya Samardzija, Marijana Chang, Andy C. M. Keck, Jadwiga Reddel, Roger R. Grimm, Christian Front Neurosci Neuroscience The quest for neuroprotective factors that can prevent or slow down the progression of retinal degeneration is still ongoing. Acute hypoxic stress has been shown to provide transient protection against subsequent damage in the retina. Stanniocalcins – STC1 and STC2 – are secreted glycoproteins that are hypoxia-regulated and were shown to be cytoprotective in various in vitro studies. Hence, we investigated the expression of stanniocalcins in the normal, degenerating and hypoxic retina. We show that the expression of Stc1 and Stc2 in the retina was detectable as early as postnatal day 10 and persisted during aging. Retinal expression of Stc2, but not Stc1, was induced in mice in an in vivo model of acute hypoxia and a genetic model of chronic hypoxia. Furthermore, we show that HIF1, not HIF2, is responsible for regulating Stc2 in cells with the molecular response to hypoxia activated due to the absence of von Hippel Lindau protein. Surprisingly, Stc2 was not normally expressed in photoreceptors but in the inner retina, as shown by laser capture microdissection and immunofluorescence data. The expression of both Stc1 and Stc2 remained unchanged in the degenerative retina with an almost complete loss of photoreceptors, confirming their expression in the inner retina. However, the absence of either Stc1 or Stc2 had no effect on retinal architecture, as was evident from retinal morphology of the respective knockout mice. Taken together our data provides evidence for the differential regulation of STC1 and STC2 in the retina and the prospect of investigating STC2 as a retinal neuroprotective factor. Frontiers Media S.A. 2022-06-23 /pmc/articles/PMC9259883/ /pubmed/35812222 http://dx.doi.org/10.3389/fnins.2022.882559 Text en Copyright © 2022 Ail, Samardzija, Chang, Keck, Reddel and Grimm. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Ail, Divya
Samardzija, Marijana
Chang, Andy C. M.
Keck, Jadwiga
Reddel, Roger R.
Grimm, Christian
Stanniocalcin2, but Not Stanniocalcin1, Responds to Hypoxia in a HIF1-Dependent Manner in the Retina
title Stanniocalcin2, but Not Stanniocalcin1, Responds to Hypoxia in a HIF1-Dependent Manner in the Retina
title_full Stanniocalcin2, but Not Stanniocalcin1, Responds to Hypoxia in a HIF1-Dependent Manner in the Retina
title_fullStr Stanniocalcin2, but Not Stanniocalcin1, Responds to Hypoxia in a HIF1-Dependent Manner in the Retina
title_full_unstemmed Stanniocalcin2, but Not Stanniocalcin1, Responds to Hypoxia in a HIF1-Dependent Manner in the Retina
title_short Stanniocalcin2, but Not Stanniocalcin1, Responds to Hypoxia in a HIF1-Dependent Manner in the Retina
title_sort stanniocalcin2, but not stanniocalcin1, responds to hypoxia in a hif1-dependent manner in the retina
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259883/
https://www.ncbi.nlm.nih.gov/pubmed/35812222
http://dx.doi.org/10.3389/fnins.2022.882559
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