Investigation of endoplasmic reticulum stress and sonic hedgehog pathway in diabetic liver injury in mice

Diabetes is a common metabolic disease which damages many organs including the liver and causes endoplasmic reticulum (ER) stress, which originates from non-folded proteins. Sonic hedgehog (Shh) pathway plays a role in liver regeneration and repair. To our knowledge, there is no study showing the re...

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Veröffentlicht in:Life sciences (1973) 2020-04, Vol.246, p.117416-13, Article 117416
Hauptverfasser: Sahinturk, Varol, Kacar, Sedat, Sahin, Erhan, Aykanat, Nuriye Ezgi Bektur
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Sprache:eng
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Zusammenfassung:Diabetes is a common metabolic disease which damages many organs including the liver and causes endoplasmic reticulum (ER) stress, which originates from non-folded proteins. Sonic hedgehog (Shh) pathway plays a role in liver regeneration and repair. To our knowledge, there is no study showing the relation between ER stress and Shh pathway in the liver in diabetes. Thus, the aim of this study was to investigate the interaction between ER stress and Shh pathway in the liver of diabetic mice. Six groups of male mice were formed as control, diabetes (streptozotocine-treated), Shh activator (SAG-treated), Shh inhibitor (SANT1-treated), diabetes + SAG and diabetes + SANT1. At the end of the experiment, mice were weighed, anaesthetized and euthanized. Blood samples were collected, livers were excised and weighed. Thereafter, blood glucose, serum ALT and AST levels, TOS and TAC levels in liver tissue were measured. ER stress marker (GRP78) and Shh pathway molecules (Gli1 and Smo) were evaluated by immunohistochemistry, H-score and western blot analyses. Besides, histopathological examination was performed. Results showed that GRP78, Gli1 and Smo were increased in liver due to Type 1 diabetes. The SAG agent decreased GRP78 and increased Gli1 and Smo, leading to liver repair, while the inhibitor SANT1 increased GRP78 and decreased Gli1and Smo, causing progression of the liver stress induced by diabetes. In conclusion, the Shh pathway is related to ER stress and may provide a new strategy for its treatment, especially liver stress induced by diabetes.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2020.117416