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Altered Expression of Vitamin D Metabolism Genes and Circulating MicroRNAs in PBMCs of Patients with Type 1 Diabetes: Their Association with Vitamin D Status and Ongoing Islet Autoimmunity
Version 1
: Received: 2 September 2023 / Approved: 4 September 2023 / Online: 5 September 2023 (11:41:35 CEST)
Version 2
: Received: 5 October 2023 / Approved: 5 October 2023 / Online: 9 October 2023 (09:28:37 CEST)
Al-Nakhle, H.; Mohsen, I.; Elnaem, B.; Alharbi, A.; Alnakhli, I.; Almoarfi, S.; Fallatah, J. Altered Expression of Vitamin D Metabolism Genes and Circulating MicroRNAs in PBMCs of Patients with Type 1 Diabetes: Their Association with Vitamin D Status and Ongoing Islet Autoimmunity. Non-Coding RNA2023, 9, 60.
Al-Nakhle, H.; Mohsen, I.; Elnaem, B.; Alharbi, A.; Alnakhli, I.; Almoarfi, S.; Fallatah, J. Altered Expression of Vitamin D Metabolism Genes and Circulating MicroRNAs in PBMCs of Patients with Type 1 Diabetes: Their Association with Vitamin D Status and Ongoing Islet Autoimmunity. Non-Coding RNA 2023, 9, 60.
Al-Nakhle, H.; Mohsen, I.; Elnaem, B.; Alharbi, A.; Alnakhli, I.; Almoarfi, S.; Fallatah, J. Altered Expression of Vitamin D Metabolism Genes and Circulating MicroRNAs in PBMCs of Patients with Type 1 Diabetes: Their Association with Vitamin D Status and Ongoing Islet Autoimmunity. Non-Coding RNA2023, 9, 60.
Al-Nakhle, H.; Mohsen, I.; Elnaem, B.; Alharbi, A.; Alnakhli, I.; Almoarfi, S.; Fallatah, J. Altered Expression of Vitamin D Metabolism Genes and Circulating MicroRNAs in PBMCs of Patients with Type 1 Diabetes: Their Association with Vitamin D Status and Ongoing Islet Autoimmunity. Non-Coding RNA 2023, 9, 60.
Abstract
Background: Vitamin D (VD) acts as an immunomodulator through the vitamin D receptor (VDR) located on pancreatic and immune cells, and deficiency is related to the development of T1DM. There is no clear understanding of the molecular mechanism by which VD is down-regulated in type 1 diabetes. So, we investigated whether VD metabolism genes are expressed differently in T1DM patients and whether serum VD levels are correlated with those genes. Additionally, we sought to assess whether miRNAs affect the expression of VD metabolism genes in PBMCs from patients with T1DM. The study also examines whether altered VD metabolism genes and miRNAs impact autoimmunity. Methods: Real-time PCR was used to detect the expression profile of gene encoding 1-hydroxylases (CYP27B1), 24-hydroxylases (CYP24A1), as well as related miRNAs in PBMCs of 30 individuals with T1DM and 23 non-diabetic subjects. ELISA test was used to determine VD, GAD65, and IA-2 expression. Results: CYP27B1 mRNA levels were down-regulated, while CYP24A1 levels were not changed in PBMCs T1DM patients than in those of healthy controls (CYP27B1, p = 0.0005, CYP24A1, p=0.205, respectively). has-miR-216b-5p expression was significantly up-regulated in T1DM while has-miR-216b-5p down-regulated compared to the control. The expression of CYP27B1 in T1DM subjects was not correlated with levels of has-miR-216b-5p, has-miR-21-5p, and VD. Interestingly, CYP27B1 mRNA concentrations in PBMCs of T1DM subjects correlated negatively with IA2 but not GAD65. Conclusions: We observed down-regulation of CYP27B1 mRNA levels and up-regulated has-miR-216b-5p in PBMCs of T1DM. However, CYP27B1 expression was not correlated with the expression of has-miR-216-5p and VD status, suggesting other mechanisms may regulate CYP27B1 expression.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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