대한신장학회

논문분류	춘계학술대회 초록집
제목	Involvement of autophagy activation in tubular cell protection against ischemia/reperfusion-induced acute kidney injury in transgenic mice overproducing omega-3 polyunsaturated fatty acids
저자	Won Min Hwang* 1, Dong Il Kim1, Kyung Ho LEE1, Se Hee Yoon1, Seung Yun Han2, Jae Ku Kang3, Sungro Yun1
출판정보	2016; 2016(1):
키워드	autophagy, Ischemia-reperfusion injury, omega 3 fatty acid
초록	Background: Acute kidney injury (AKI) is common clinical event and has high mortality rate despite advanced curative strategies. Several studies found that omega-3 polyunsaturated fatty acid(PUFA) diet reduces kidney dysfunction followed by ischemic injury. However, oral appliance of omega-3 PUFA to experimental animals, in fact, can cause much variability arisen from diet procedure. fat-1 transgenic mouse produce abundant omega-3 PUFA, resulting in balanced omega-6 : omega-3 ratio than wild type mouse. The purpose of this study, therefore, is to see whether omega-3 PUFA has advantages in ischemia/reperfusion(I/R)-induced AKI using fat-1 transgenic mice. In addition, we investigated the involvement of autophagy process as a possible underlying mechanism of these protection. Methods: Bilateral kidneys of experimental animals (fat-1 mice and C57BL/6 mice as control) were subjected to 30 min of Ischemia. After 24hours and 72 hours of reperfusion, animals were sacrificed. The effects of omega-3 PUFA on IR-induced AKI were evaluated in terms of serological marker for renal function, kidney injury marker (i.e., Kim-1), tubular morphology, and inflammatory cell infiltration. Finally, autophagy status in renal tubular cells with or without IR-induction was assessed by confocal microscopic observation. Results: After I/R-induced AKI, fat-1 mice showed the reduced level of serum BUN and creatinine compared with control. Furthermore, Kim-1 levels and morphological damage of renal tubule were reduced. Neutrophil infiltration into renal cortex were minimized in fat-1 mice compared with control. Interestingly, immunohistochemical detection of autophagosomes revealed that autophagy were activated in fat-1 mice kidney at basal status. After I/R-induced AKI challenges, autophagy levels were unchanged in fat-1 mice. Activated autophagy in basal status might contributed to tubular protection against AKI. Conclusion: Long-term and high dose of omega-3 supplement may protect renal function and structures against AKI via basal autophagy activation.
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