Role of autophagy and evaluation the effects of microRNAs 214, 132, 34c and prorenin receptor in a rat model of focal segmental glomerulosclerosis
| Autor: | Mukadder Ayse Bilgic, Fatma Helvacioglu, Ali Akcay, Nuket Bavbek Ruzgaresen, Derya Yildirim, Zehra Firat Karagoz, Onur Bender |
|---|---|
| Přispěvatelé: | Fırat Karagöz, Zehra |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Vacuolar Proton-Translocating ATPases ATG5 Focal segmental glomerulosclerosis Receptors Cell Surface miR-214 030226 pharmacology & pharmacy miR-132 General Biochemistry Genetics and Molecular Biology Podocyte Rats Sprague-Dawley Pathogenesis 03 medical and health sciences 0302 clinical medicine Autophagy Animals Medicine Prorenin Receptor General Pharmacology Toxicology and Pharmaceutics Cells Cultured ATP6AP2 Glomerulosclerosis Focal Segmental business.industry Prorenin General Medicine medicine.disease Rats Blot MicroRNAs 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Cancer research miR-34c business |
| Zdroj: | Life Sciences |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2021.119671 |
| Popis: | Aims Focal segmental glomerulosclerosis (FSGS) is the common cause of chronic renal disease worldwide. Although there are many etiologic factors which have common theme of podocyte injury conclusive etiology is not clearly understood. In this study, we aimed to explore the role of autophagy in the pathogenesis of podocyte injury, which is the key point in disease progression, and the roles of intrarenal microRNAs and the prorenin receptor (PRR) in the 5/6 nephrectomy and adriamycin nephropathy models of FSGS. Main methods For experimental FSGS model, 5/6 nephrectomy and adriamycin nephropathy models were created and characterized in adult Sprague Dawley rats. Microarray analysis was performed on FSGS and control groups that was confirmed by q-RT-PCR. Beclin1, LC3B, PRR, ATG7 and ATG5 expression were evaluated by western blotting and immunohistochemistry. Also, Beclin1 and PRR expression were measured by ELISA. Glomerular podocyte isolation was performed and autophagic activity was evaluated in podocytes before and after transfection with miRNA mimic and antagonists. Key findings Glomerular expression of Beclin1, LC3B, PRR, ATG7 and ATG5 were significantly lower in the 5/6 nephrectomy than adriamycin nephropathy group and in both groups lower when compared to control groups. Western blot results were consistent with immunohistochemical data. Electron microscopy revealed signs of impaired autophagy in FSGS. Autophagic activity decreased significantly after miR-214, miR-132 and miR-34c mimics and increased after transfection with antagonists. Significance These results showed that the role of autophagic activity and decreased expression of PRR in FSGS pathogenesis and miR-34c, miR-132 and miR-214 could be a potential treatment strategy by regulating autophagy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect