Phenotypical and biochemical characterization of murine psoriasiform and fibrotic skin disease models in Stabilin-deficient mice
Stabilin-1 (Stab1) and Stabilin-2 (Stab2) are scavenger receptors expressed by liver sinusoidal endothelial cells (LSECs). The Stabilin-mediated scavenging function is responsible for regulating the molecular composition of circulating blood in mammals. Stab1 and Stab2 have been shown to influence f...
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| Hauptverfasser: | , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
September 2024
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| In: |
FEBS Open Bio
Year: 2024, Jahrgang: 14, Heft: 9, Pages: 1455-1470 |
| ISSN: | 2211-5463 |
| DOI: | 10.1002/2211-5463.13857 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1002/2211-5463.13857 Verlag, kostenfrei, Volltext: http://onlinelibrary.wiley.com/doi/abs/10.1002/2211-5463.13857 
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| Verfasserangaben: | Jessica Krzistetzko, Cyrill Géraud, Christof Dormann, Anna Riedel and Thomas Leibing |
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| 245 | 1 | 0 | |a Phenotypical and biochemical characterization of murine psoriasiform and fibrotic skin disease models in Stabilin-deficient mice |c Jessica Krzistetzko, Cyrill Géraud, Christof Dormann, Anna Riedel and Thomas Leibing |
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| 520 | |a Stabilin-1 (Stab1) and Stabilin-2 (Stab2) are scavenger receptors expressed by liver sinusoidal endothelial cells (LSECs). The Stabilin-mediated scavenging function is responsible for regulating the molecular composition of circulating blood in mammals. Stab1 and Stab2 have been shown to influence fibrosis in liver and kidneys and to modulate inflammation in atherosclerosis. In this context, circulating and localized TGFBi and POSTN are differentially controlled by the Stabilins as their receptors. To assess Stab1 and Stab2 functions in inflammatory and fibrotic skin disease, topical Imiquimod (IMQ) was used to induce psoriasis-like skin lesions in mice and Bleomycin (BLM) was applied subcutaneously to induce scleroderma-like effects in the skin. The topical treatment with IMQ, as expected, led to psoriasis-like changes in the skin of mice, including increased epidermal thickness and significant weight loss. Clinical severity was reduced in Stab2-deficient compared to Stab1-deficient mice. We did not observe differential effects in the skin of Stabilin-deficient mice after bleomycin injection. Interestingly, treatment with IMQ led to a significant increase of Stabilin ligand TGFBi plasma levels in Stab2−/− mice, treatment with BLM resulted in a significant decrease in TGFBi levels in Stab1−/− mice. Overall, Stab1 and Stab2 deficiency resulted in minor alterations of the disease phenotypes accompanied by alterations of circulating ligands in the blood in response to the disease models. Stabilin-mediated clearance of TGFBi was altered in these disease processes. Taken together our results suggest that Stabilin deficiency-associated plasma alterations may interfere with preclinical disease severity and treatment responses in patients. | ||
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