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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2022.882559/full |
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| author | Divya Ail Divya Ail Divya Ail Marijana Samardzija Andy C. M. Chang Jadwiga Keck Roger R. Reddel Christian Grimm Christian Grimm Christian Grimm |
| author_facet | Divya Ail Divya Ail Divya Ail Marijana Samardzija Andy C. M. Chang Jadwiga Keck Roger R. Reddel Christian Grimm Christian Grimm Christian Grimm |
| author_sort | Divya Ail |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T08:16:50Z |
| format | Article |
| id | doaj.art-29ca4b7485a24380bbac9393ad53a957 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-12T08:16:50Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-29ca4b7485a24380bbac9393ad53a9572022-12-22T00:31:32ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-06-011610.3389/fnins.2022.882559882559Stanniocalcin2, but Not Stanniocalcin1, Responds to Hypoxia in a HIF1-Dependent Manner in the RetinaDivya Ail0Divya Ail1Divya Ail2Marijana Samardzija3Andy C. M. Chang4Jadwiga Keck5Roger R. Reddel6Christian Grimm7Christian Grimm8Christian Grimm9Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, FranceLab for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, SwitzerlandNeuroscience Center Zurich (ZNZ), University of Zurich, Zurich, SwitzerlandLab for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, SwitzerlandFaculty of Medicine and Health, Children’s Medical Research Institute, University of Sydney, Westmead, NSW, AustraliaLab for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, SwitzerlandNeuroscience Center Zurich (ZNZ), University of Zurich, Zurich, SwitzerlandLab for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, SwitzerlandNeuroscience Center Zurich (ZNZ), University of Zurich, Zurich, SwitzerlandZurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, SwitzerlandThe 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.https://www.frontiersin.org/articles/10.3389/fnins.2022.882559/fullstanniocalcin1 (Stc1)stanniocalcin2 (Stc2)hypoxiahypoxia-inducible factor 1a (HIF1a)retinal stress |
| spellingShingle | Divya Ail Divya Ail Divya Ail Marijana Samardzija Andy C. M. Chang Jadwiga Keck Roger R. Reddel Christian Grimm Christian Grimm Christian Grimm Stanniocalcin2, but Not Stanniocalcin1, Responds to Hypoxia in a HIF1-Dependent Manner in the Retina Frontiers in Neuroscience stanniocalcin1 (Stc1) stanniocalcin2 (Stc2) hypoxia hypoxia-inducible factor 1a (HIF1a) retinal stress |
| 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 | stanniocalcin1 (Stc1) stanniocalcin2 (Stc2) hypoxia hypoxia-inducible factor 1a (HIF1a) retinal stress |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2022.882559/full |
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