대한신장학회

논문분류	춘계학술대회 초록집
제목	Angiotensin II Modulates p130Cas of Podocytes by the Suppression of AMP-Activated Protein Kinase
저자	Tae-Sun Ha*, Hye-Young Park1, Su-Bin Seong1
출판정보	2016; 2016(1):
키워드	AMP-activated Protein Kinase, Angiotensin II, p130Cas, Podocyte
초록	Background: Angiotensin II (Ang II) induces the pathological process of vascular structures, including renal glomeruli by hemodynamic and nonhemodynamic direct effects. In kidney, Ang II plays an important role in the development of proteinuria by the modification of podocyte molecules. p130Cas localizes diffusely to the cytoplasm with accumulation at ends of F-actin stress fibers in podocyte foot processes, where focal adhesion proteins and kinases (FAKs) connect docking proteins, including integrin and p130Cas to the glomerular basement membrane at basal aspect, and CD2AP and p130Cas to the slit diaphragm insertion site between foot processes. Therefore, p130Cas protein plays an important role in maintaining the glomerular permeability by connecting podocyte actin cytoskeleton to GBM and SD. We have previously found that Ang II suppressed podocyte AMP-activated protein kinase (AMPK) via Ang II type 1 receptor and MAPK signaling pathway. In the present study, we investigated the roles of AMPK on the changes of p130Cas of podocyte by Ang II. Methods: We cultured mouse podocytes and treated them with various concentrations of Ang II and AMPK-modulating agents and analyzed the changes of p130Cas by confocal imaging and Western blotting. Results: In immunofluorescence study, Ang II decreased the intensity of p130Cas and changed its localization from peripheral cytoplasm into peri-nuclear areas in a concentrated pattern in podocytes. Ang II also reduced the amount of p130Cas in time and dose-sensitive manners. AMPK activators, metformin and AICAR, restored the suppressed and mal-localized p130Cas significantly, whereas, compound C, an AMPK inhibitor, further aggravated the changes of p130Cas. Losartan, an Ang II type 1 receptor antagonist, recovered the abnormal changes of p130Cas suppressed by Ang II. Conclusion: These results suggest that Ang II induces the relocalization and suppression of podocyte p130Cas by the suppression of AMPK via Ang II type 1 receptor, which would contribute to disturbed interaction of p130Cas with other adjacent proteins could induce podocyte hyperpearmeability.
원문(PDF)	PDF 원문보기

간행물 검색

대한신장학회 회원관리 규정