Genetic and epigenetic-sensitive regulatory network in immune response: a putative link between HLA-G and diabetes

Sommese, Linda; Benincasa, Giuditta; Schiano, Concetta; Marfella, Raffaele; Grimaldi, Vincenzo; Sorriento, Antonio; Lucchese, Roberta; Fiorito, Carmela; Sardu, Celestino; Nicoletti, Giovanni Francesco; Napoli, Claudio

doi:10.1080/17446651.2019.1620103

Cited by 13 publications

(8 citation statements)

References 70 publications

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“…Since diabetes is often associated with obesity, the genes related to obesity, such as FTO and MC4R, are often connected with diabetes. Any changes in Pdx1 and Glut4 genes’ functions predominantly play a vital role in developing Type 1 diabetes [ 59 ]. Epigenetic alterations such as histone methylation, acetylation, phosphorylation, DNA methylation, chromatin remodeling, and oxidative stress play an essential role in promoting and progressing diabetic mellitus.…”

Section: Diabetes and Cholesterolmentioning

confidence: 99%

An Overview on the Therapeutic Function of Foods Enriched with Plant Sterols in Diabetes Management

et al. 2021

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Diabetes is one of the most significant health issues across the world. People identified with diabetes are more vulnerable to various infections and are at a greater risk of developing cardiovascular diseases. The plant-based food we consume often contains many sterol-based bioactive compounds. It is well documented that these compounds could effectively manage the processes of insulin metabolism and cholesterol regulation. Insulin resistance followed by hyperglycemia often results in oxidative stress level enhancement and increased reactive oxygen species production. At the molecular level, these changes induce apoptosis in pancreatic cells and hence lead to insulin insufficiency. Studies have proved that plant sterols can lower inflammatory and oxidative stress damage connected with DNA repair mechanisms. The effective forms of phyto compounds are polyphenols, terpenoids, and thiols abundant in vegetables, fruits, nuts, and seeds. The available conventional drug-based therapies for the prevention and management of diabetes are time-consuming, costly, and with life-threatening side effects. Thereby, the therapeutic management of diabetes with plant sterols available in our daily diet is highly welcome as there are no side effects. This review intends to offer an overview of the present scenario of the anti-diabetic compounds from food ingredients towards the therapeutic beneficial against diabetes.

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Section: Diabetes and Cholesterolmentioning

confidence: 99%

An Overview on the Therapeutic Function of Foods Enriched with Plant Sterols in Diabetes Management

et al. 2021

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“…For instance, expression of Major Histocompatibility Complex, Class I, G (HLA-G), a nonclassical MHC-class I molecule, decreases in adult ASCs together with immunotolerance through inhibition of NK, allogeneic T-cell responses and dendritic cells (DC) [10]. HLA-G is also involved in epigenetic regulation of tolerance to cardiac ischemia as well as susceptibility to infection after kidney transplantation [11][12][13]. A well-known immune checkpoint (IC) with immunosuppressive functions is the Programmed death-ligand 1 (PD-L1) [14].…”

Section: Introductionmentioning

confidence: 99%

MiR-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms

et al. 2021

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Adipose-derived mesenchymal stem cells (ASCs) are promising therapeutic tools in regenerative medicine because they possess self-renewal, differentiation and immunomodulatory capacities. After isolation, ASCs are passaged multiple times in vitro passages to obtain a sufficient amount of cells for clinical applications. During this time-consuming procedure, ASCs become senescent and less proliferative, compromising their clinical efficacy. Here, we sought to investigate how in vitro passages impact ASC proliferation/senescence and expression of immune regulatory proteins. MicroRNAs are pivotal regulators of ASC physiology. Particularly, miR-200c is known to maintain pluripotency and targets the immune checkpoint Programmed death-ligand 1 (PD-L1). We therefore investigated its involvement in these critical characteristics of ASCs during in vitro passages. We found that when transiently expressed, miR-200c-3p promotes proliferation, maintains stemness, and contrasts senescence in late passaged ASCs. Additionally, this miRNA modulates PD-L1 and Indoleamine 2,3-Dioxygenase (IDO1) expression, thus most likely interfering with the immunoregulatory capacity of ASCs. Based on our results, we suggest that expression of miR-200c-3p may prime ASC towards a self-renewing phenotype by improving their in vitro expansion. Contrarily, its inhibition is associated with senescence, reduced proliferation and induction of immune regulators. Our data underline the potential use of miR-200c-3p as a switch for ASCs reprogramming and their clinical application.

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“…The clinical role of HLA-G has been widely explored in various pathophysiological conditions, such as organ transplantation, viral infection, autoimmune and inflammatory diseases, and cancer [13,14,[26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

“…In the last years, advanced network-oriented analysis unveiled specific molecular pathways underlying CHD-related endophenotypes, mainly endothelial inflammation, providing novel insight in disease pathobiology [ 8 – 12 ]. Some authors emphasized the key role of DNA methylation in regulating the human leukocyte antigen-G (HLA-G) gene expression involved in inflammatory-related pathways underlying CHD onset [ 13 , 14 ]. HLA-G belongs to nonclassical Ib antigen of the major histocompatibility complex (MHC) representing a crucial immune checkpoint for the maintenance of self-tolerance and modulation of innate immune response [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of DNA methylation profile of HLA-G gene and imaging in coronary heart disease: Pilot study

et al. 2020

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Immune endothelial inflammation, underlying coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features. Methods Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score = 0, uninjured coronaries and with no obstructive CHD (no critical stenosis, NCS) were considered as control subjects (n = 18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software. Results For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p = 0.05) of HLA-G gene in

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Genetic and epigenetic-sensitive regulatory network in immune response: a putative link between HLA-G and diabetes

Cited by 13 publications

References 70 publications

An Overview on the Therapeutic Function of Foods Enriched with Plant Sterols in Diabetes Management

An Overview on the Therapeutic Function of Foods Enriched with Plant Sterols in Diabetes Management

MiR-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms

Integrated analysis of DNA methylation profile of HLA-G gene and imaging in coronary heart disease: Pilot study

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