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dc.contributor.authorHachim, Mahmood Yaseen
dc.date.accessioned2022-01-19T05:22:44Z
dc.date.available2022-01-19T05:22:44Z
dc.date.issued2021
dc.identifier.other204-2021.52
dc.identifier.urihttps://repository.mbru.ac.ae/handle/1/746
dc.description.abstractAbstract: Iron overload promotes the generation of reactive oxygen species (ROS). Pancreatic β-cells can counter oxidative stress through multiple anti-oxidant responses. Herein, RNA-sequencing was used to describe the expression profile of iron regulatory genes in human islets with or without diabetes. Functional experiments including siRNA silencing, qPCR, western blotting, cell viability, ELISA and RNA-sequencing were performed as means of identifying the genetic signature of the protective response following iron overload-induced stress in human islets and INS-1. FTH1 and FTL genes were highly expressed in human islets and INS-1 cells, while hepcidin (HAMP) was low. FXN, DMT1 and FTHL1 genes were differentially expressed in diabetic islets compared to control. Silencing of Hamp in INS-1 cells impaired insulin secretion and influenced the expression of β-cell key genes. RNA-sequencing analysis in iron overloaded INS-1 cells identified Id1 and Id3 as the top down-regulated genes, while Hmox1 was the top upregulated. Expression of ID1, ID3 and HMOX1 was validated at the protein level in INS-1 cells and human islets. Differentially expressed genes (DEGs) were enriched for TGF-β, regulating stem cells, ferroptosis, and HIF-1 signaling. Hmox1-silenced cells treated with FAC elevated the expression of Id1 and Id3 expression than untreated cells. Our findings suggest that HMOX1, ID1 and ID3 define the response mechanism against iron-overload-induced stress in β-cells.en_US
dc.language.isoenen_US
dc.subjectDiabetesen_US
dc.subjectIron-overload Insulinen_US
dc.subjectHuman isletsen_US
dc.subjectINS-1 cellsen_US
dc.subjectHMOX1en_US
dc.subjectID1en_US
dc.subjectID3en_US
dc.titleHeme Oxygenase-1 (HMOX-1) and inhibitor of differentiation proteins (ID1, ID3) are key response mechanisms against iron-overload in pancreatic β-cellsen_US
dc.typeArticleen_US


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