Screen Micrornas In Systemic Lupus Erythematosus During Its Active Phase And Therapy

Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease characterized by having autoantibodies against several self-antigens and causing damage to various organs or systems, including skin, joints, kidneys and the central nervous system, etc. The pathogenesis of SLE is correlated with both genetic predispositions and environmental influences. The contribution of these two factors may differ between individuals, but the resulting malfunctions in the immune system and the production of autoantibodies play an important role in the pathogenesis of SLE. Previous studies have revealed that symptoms resembling SLE appear in a variety of immunological disorders, but the mechanisms of SLE pathogenesis remain unknown and the cause of the diversity of symptoms is unclear. MiRNAs are short noncoding RNA molecules that inhibit gene expression through incomplete base pairing with the 30-untranslated region (30-UTR) of target mRNAs. Many articles have been published showing a probable link between miRNAs and different human diseases. Until now, there is no report of SLE research from the aspect of miRNA. This study attempts to reveal the involvement of miRNAs and their targets in SLE pathogenesis. We applied miRNA microarray chips to screen differentially expressed miRNAs in PMBC of SLE patients and renal biopsies of lupus nephritis patients. PART I MICROARRAY ANALYSIS OF MICRORNA EXPRESSION IN PERIPHERAL BLOOD CELLS OF SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTSObject: To further understand the pathogenesis of SLE and clarify the relationship between SLE and microRNA. Method: This study describes a comparison between the microRNA profile of the systemic lupus erythematosus (SLE) patients and the controls. Peripheral blood mononuclear cells (PBMC) were isolated from blood samples of 23 SLE patients, 10 idiopathic thrombocytopenic purpura (ITP) patients and 10 health controls. MicroRNA isolated from PBMC was applied to the miRNA microarray chip and the results were verified by Northern blot analysis. Results: The miRNA microarray chip analysis identified 16 miRNAs differentially expressed in SLE. The chip results were confirmed by northern blot analysis. Conclusion: This work indicates that miRNAs are potential diagnosis biomarkers and probable factors involved in the pathogenesis of SLE. PART II COMPREHENSIVE ANALYSIS OF MICRORNA EXPRESSION PATTERNS IN RENAL BIOPSIES OF LUPUS NEPHRITIS PATIENTSObjective: To investigate differentially expressed microRNAs in lupus nephritis. Methods: Collected biopsies of 5 patients with lupus nephritis and 3 renal cortexes of tissue eumorphism patients as normal control group. The study of microRNAs differential expression was carried by MicroRNA array and Real-time RT-PCR. Results: There were 66 microRNAs differential expression of which 36 up-regulated and 30 down-regulated in lupus nephritis. Hsa-miR-657 , hsa-miR-615 were selected for relative quantification by Real-time RT-PCR. It showed that the quantity of hsa-miR-657 was increased 1.558 times and the quantity of hsa-miR-615 was decreased 0.346 times in lupus nephritis compared with the control. Conclusions: The differential expression of miRNAs in lupus nephritis indicates that miRNAs are potential diagnosis biomarkers and probable factors involved in the pathogenesis of lupus nephritis. MicroRNAs may help to diagnosis, treat and prevent lupus nephritis.