Sanaa Eissa1, Marwa Matboli2, Rowaida Aboushahba2, Miram M Bekhet3, Yasser Soliman4. 1. Oncology Diagnostic Unit, Medical Biochemistry and Molecular biology Department, Faculty of Medicine, Ain Shams University, P.O. box 11381, Abbassia, Cairo, Egypt. Electronic address: Dr_sanaa_eissa@yahoo.com. 2. Oncology Diagnostic Unit, Medical Biochemistry and Molecular biology Department, Faculty of Medicine, Ain Shams University, P.O. box 11381, Abbassia, Cairo, Egypt. 3. Diabetes and endocrinology Unit, Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. 4. Nephrology Unit, Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Abstract
BACKGROUND: A potential approach adopted in the current study is to design a panel based on in silico retrieval of novel miRNAs related to diabetic kidney disease and to evaluate its usefulness in disease diagnosis. PATIENT AND METHODS: In the current study, we measured the differential expression of a 6 miRNA panel in urine pellet and exosome in an initial screening group using syber green-based PCR array. Also, we performed pathway enrichment analysis of the key target genes of these miRNAs. Finally, we selected the most significantly up-regulated miRNAs in DKD, exosomal miR-15b, miR-34a and miR-636, that were measured by real-time PCR in a larger independent set of 180 participants to evaluate their usefulness as novel urine biomarkers for diagnosis diabetic kidney disease. RESULTS: PCR array analysis showed that miR-15b, miR-34a, and miR-636 were upregulated in both urine pellet and exosome of type 2DKD patients. qRT-PCR validation in the larger independent set of participants confirmed the significant up-regulation of these urinary exosomal miRs (P<0.001). Notably, a positive correlation was found between these miRs, serum creatinine and urinary protein creatinine ratio. The sensitivity of this miRs based panel in urine exosomes reached 100% in diagnosis of DKD. CONCLUSION: We identified urinary exosomal miR-15b, miR-34a, and miR-636 as a novel diagnostic panel and a major contributor in the pathogenesis of diabetic kidney disease.
BACKGROUND: A potential approach adopted in the current study is to design a panel based on in silico retrieval of novel miRNAs related to diabetic kidney disease and to evaluate its usefulness in disease diagnosis. PATIENT AND METHODS: In the current study, we measured the differential expression of a 6 miRNA panel in urine pellet and exosome in an initial screening group using syber green-based PCR array. Also, we performed pathway enrichment analysis of the key target genes of these miRNAs. Finally, we selected the most significantly up-regulated miRNAs in DKD, exosomal miR-15b, miR-34a and miR-636, that were measured by real-time PCR in a larger independent set of 180 participants to evaluate their usefulness as novel urine biomarkers for diagnosis diabetic kidney disease. RESULTS: PCR array analysis showed that miR-15b, miR-34a, and miR-636 were upregulated in both urine pellet and exosome of type 2DKD patients. qRT-PCR validation in the larger independent set of participants confirmed the significant up-regulation of these urinary exosomal miRs (P<0.001). Notably, a positive correlation was found between these miRs, serum creatinine and urinary protein creatinine ratio. The sensitivity of this miRs based panel in urine exosomes reached 100% in diagnosis of DKD. CONCLUSION: We identified urinary exosomal miR-15b, miR-34a, and miR-636 as a novel diagnostic panel and a major contributor in the pathogenesis of diabetic kidney disease.
Authors: Mitzi M Gonzales; Sudarshan Krishnamurthy; Valentina Garbarino; Ali S Daeihagh; Gregory J Gillispie; Gagan Deep; Suzanne Craft; Miranda E Orr Journal: Mech Ageing Dev Date: 2021-10-21 Impact factor: 5.498
Authors: Taylor C Peak; Gati K Panigrahi; Prakash P Praharaj; Yixin Su; Lihong Shi; Jacqueline Chyr; José Rivera-Chávez; Laura Flores-Bocanegra; Ravi Singh; Donald J Vander Griend; Nicholas H Oberlies; Bethany A Kerr; Ashok Hemal; Rhonda L Bitting; Gagan Deep Journal: Mol Carcinog Date: 2019-11-01 Impact factor: 4.784