PhD Scientific Days 2018

Oral presentations: Pathology

Functional investigation of miR-17-5p inhibition in kidney ischemia-reperfusion injury in mice

Előadó neve

Dr. Kaucsár, Tamás

Előadó munkahelye

Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary

Előadó telefonszáma

06 20 666 3829

Előadó e-mail címe

kaucsar.tamas@med.semmelweis-univ.hu

Az előadás címe

Functional investigation of miR-17-5p inhibition in kidney ischemia-reperfusion injury in mice

Szerző(k) neve és munkahelye

Tamás Kaucsár1,2, Pál Tod2, Mária Godó2, Johan Lorenzen3, Thomas Thum3, Gábor Szénási2, Péter Hamar1,2
1 Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary
2 Institute of Pathophysiology, Semmelweis University, Budapest, Hungary
3 Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany

Bemutatás módja

Szóbeli

Szekció

Oral presentations: Pathology

Language of the presentation

Hungarian

Témacsoport

pathology and pathophysiology (non-oncology)

Összefoglaló szövege

Introduction: One of the most common causes of acute kidney injury (AKI) is ischemia-reperfusion (IR), which increases the risk of renal fibrosis and chronic kidney disease. Our group has previously described the activation of the pro-proliferative and anti-apoptotic miR-17-5p in IR induced AKI.
Aims: Our aim was to investigate the function of miR-17-5p in IR-induced renal fibrosis in mice.
Methods: AKI was induced in the left kidneys of C57BL/6N mice with 20-minute ischemia, without the removal of the right intact kidney. One day before the IR operation, mice were given miR-17-5p silencing (17-LNA-IR group, N = 10) or scrambled sequence (SCR-IR group, N = 10) locked nucleic acid (LNA) modified antisense oligonucleotides (30 mg / kg, ip). On the 7th reperfusion day, the efficacy of the miR-17-5p inhibition was evaluated in the injured and control kidneys (qPCR). We investigated the extent of tubular damage in histological sections (PAS, HE) and KIM1 mRNA, the miR-17-5p-target p21 mRNA expression, fibrosis (FN1 mRNA), inflammation (TNFα mRNA), the oxidative stress response (NRF2 mRNA), and the cell-proliferation (PCNA mRNA) with real-time PCR.
Results: At the 7th reperfusion day, specific LNA inhibition prevented the increase in miR-17-5p expression (1.62x, p <0.01, SCR-IR vs. non-IR) in the damaged kidneys (0.49x, p < 0.0001; 17-LNA-IR vs. SCR-IR). The inhibition of miR-17-5p following IR had no significant effect either on the histological damage, or on increased KIM1 (83.2x, p <0.0001), FN1 (8.6x, p <0.0001), TNFα (5.8x, p < 0.0001), NRF2 (1.4x, p <0.01), PCNA (1.3x, p <0.05), and p21 (3.8x, p <0.0001) mRNA levels.
Conclusion: While miR-17-5p could have renoprotective effects, our findings suggest that miR-17-5p inhibition has no significant effects on the IR-induced AKI outcome. (ÚNKP-17-4/EMMI)

Data of the presenter

Doctoral School: ÚNKP-17-4, A-VI-2 (Basic Medicine)
Program: Experimental nephrology
Principal investigator: Péter Hamar
E-mail address: kaucsar.tamas@med.semmelweis-univ.hu

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

2793

Authors (legacy)

Tamás Kaucsár1,2, Pál Tod2, Mária Godó2, Johan Lorenzen3, Thomas Thum3, Gábor Szénási2, Péter Hamar1,2
1 Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary
2 Institute of Pathophysiology, Semmelweis University, Budapest, Hungary
3 Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany