2013년 한국분자세포생물학회(KSMCB 2013), 2013, 02, 120─120

Inhibition of aerobic glycolysis prevents TGF-b1induced EMT and dedifferentiation of renal cells

DaeYeon Lee, Gyu Hee Kim, Keon Jae Park, Eun Ae Jeong, Ji Yeon Kim, WonHo Kim

Abstract

Aerobic glycolysis is considered as a metabolic adaptation of cancer cells for long times. However it is hardly known to date whether aerobic glycolysis might be involved in renal fibrosis during nephropathy. From previous metabolome analysis data, we know that the levels of lactate and pyruvate were elevated in the urine of STZ-injected mice compared to control mice. We also found that the mRNA and protein level of lactate dehydrogenase A (LDHA) were up-regulated in the kidney tissue of STZ mice. In addition we observed that the lactate level increased in the culture media of TGF-？1 treated rat renal cells, NRK-52E and RMC, which is associated with the increase of ？-SMA and fibronectin expression. Interestingly, the blocking of aerobic glycolysis pathway using oxamate and dichloroacetate (DCA), which are specific inhibitors of LDHA and PDK1 respectively, significantly reduced TGF-？1-induced ？-SMA and fibronectin expression. These results suggest that aerobic glycolysis may be involved in the development of renal fibrosis during diabetic nephropathy and the inhibition aerobic glycolysis may be also promised as a novel preventing and therapeutic approach for diabetic nephropathy.

• 본 연구는 질병관리본부 연구개발과제(과제번호 2013-NG64002-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2013-NG64002-00) by Research of Korea Centers for Disease Control and Prevention.