2013년도 생화학분자생물학회 연례국제학술대회, 2013, 02, 114─114

A critical role of activating tranion factor-3 on TNF-a-mediated MCP-1 expression and extracellular matrix accumulation in proximal tubular cells

GyuHee Kim, Ji Yeon Kim, Keon Jae Park, Eun Ae Jeong, Dae Yeon Lee, WonHo Kim

Abstract

Diabetic nephropathy(DN) is characterized by fibrosis of renal glomerulus and tubulointerstitial region. However, the exact molecular mechanisms by which diabetes may initiate or exacerbate chronic kidney disease remain elusive. Here, we investigated whether ATF3 affects diabetic kidney failure and especially, expression of inflammatory factors and macrophage infiltration during the processing of fibrosis. STZ-induced DN rats exhibited renal dysfunction, as evidenced by increased volume of renal glomerulus, thickened basement membrane, and increased mesenterium mass. ATF3 and MCP-1 expression was correlatively increased in STZ-treated renal tissue. In NRK-52E cells, TNF-？-induced fibrotic gene expression was potentiated by ATF3, which were attenuated by ATF3 siRNA. Also, ATF3 directly activates the tranional activity of MCP-1 promoter by NF-kB-dependent pathway. The macrophage cells cocultured in upper chamber migrated into the TNF-？？treated NRK-52E cells of lower chamber, which were abolished by ATF3 depletion or anti-TNF-？ antibody. Here, we know that ATF3 may play as an important regulator of renal fibrosis by enhancing ECM accumulation and macrophage infiltration, and thereby reveals a new aspect of the therapeutic mechanisms involved in DN

• 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.