The dysregulation of mitochondrial homeostasis-related genes could be involved in the decrease of mtDNA copy number in systemic lupus erythematosus patients.
Giada De Benedittis, Andrea Latini, Chiara Morgante, Carlo Perricone, Fulvia Ceccarelli, Giuseppe Novelli, Lucia Novelli, Cinzia Ciccacci, Paola Borgiani
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引用次数: 0
Abstract
Systemic lupus erythematosus (SLE) is a chronic multifactorial autoimmune disease. It is now widely demonstrated that oxidative stress (OS) plays an important role in the modulation of the pathogenesis of this disease. Mitochondrial DNA (mtDNA) is highly vulnerable to OS and it is known a decrease of mtDNA copy number in SLE patients. However, to date, it has not been investigated if this decrease is associated with a dysregulation of mitochondrial homeostasis genes. Our aim is to evaluate the amount of mtDNA copy number and the expression of the genes more involved in the mitochondrial homeostasis pathways, in peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls. We analysed the amount of mtDNA in PBMCs of 72 SLE patients and 61 healthy controls by qPCR. Then, we investigated the expression variability of TFAM and SIRT1 (biogenesis), MFN1 and MFF (fusion/fission) and PRKN2 (mitophagy) genes in a subgroup of SLE patients and healthy controls. Interestingly, we have observed a highly significant decrease in mtDNA copies in SLE patients compared to healthy controls (P < 0.0001). In addition, we have shown that the expression levels of SIRT1, MFN1 and PRKN2 genes were significantly decreased in SLE patients with respect to healthy controls (P = 0.00001 for SIRT1, P = 0.0150 for MFN1 and P = 0.0009 for PRKN2). Lastly, we have reported a positive correlation between PRKN2 expression level and mtDNA copy number (P = 0.019, r = 0.475). In conclusion, our data confirm the impairment of mtDNA copy number in the disease and show for the first time a dysregulation of the mitochondrial homeostasis genes. These results could provide additional support to the important role of mitochondria in SLE development.
期刊介绍:
IMMUNOLOGIC RESEARCH represents a unique medium for the presentation, interpretation, and clarification of complex scientific data. Information is presented in the form of interpretive synthesis reviews, original research articles, symposia, editorials, and theoretical essays. The scope of coverage extends to cellular immunology, immunogenetics, molecular and structural immunology, immunoregulation and autoimmunity, immunopathology, tumor immunology, host defense and microbial immunity, including viral immunology, immunohematology, mucosal immunity, complement, transplantation immunology, clinical immunology, neuroimmunology, immunoendocrinology, immunotoxicology, translational immunology, and history of immunology.