Angiopoietin-like protein 3 regulates the motility and permeability of podocytes by altering nephrin expression in vitro.
It is well known that podocyte injury plays a vital role in massive proteinuria. The increase of podocyte motility results in podocyte foot process (FP) effacement, a typical form of podocyte injury. Our previous studies demonstrated that glomerular podocytes can express angiopoietin-like protein 3 (ANGPTL3) and that the increase of ANGPTL3 in dysfunctional glomerulus is correlated with podocyte FP effacement. Little is known, however, about the role of ANGPTL3 in podocyte injury. In this study, we investigated ANGPTL3's effect on the motility and permeability of podocytes and on the expression of nephrin, a key molecule in podocytes. By scrape-wound and transwell migration assay, we found that ANGPTL3 over-expression significantly increased podocyte motility, whereas after ANGPTL3 knockdown by RNA interference, motility remained the same as that of the control group. Adriamycin (ADR) treatment significantly promoted podocyte motility. However, the same dose of ADR treatment could not promote motility after the knockdown of ANGPTL3. In addition, we assayed the diffusion of FITC-BSA across the podocytes' monolayer to investigate whether ANGPTL3 could promote protein loss by means of an increase in podocyte motility. The results showed that the changes in the FITC-BSA permeability of the podocytes corresponded to changes in motility. Furthermore, we found that ANGPTL3 over-expression dramatically increased the expression of nephrin but that the up-regulation of nephrin induced by ADR was significantly inhibited when ANGPTL3 was diminished by RNAi. In conclusion, we found ANGPTL3 to be capable of regulating the motility and permeability of podocytes and that the mechanism of ANGPTL3's regulation could be associated with the altered expression of nephrin.
Gao
Xia
X
Department of Nephrology, Children's Hospital of Fudan University, Shanghai, China.
Xu
Hong
H
Liu
Haimei
H
Rao
Jia
J
Li
Yunling
Y
Zha
Xiliang
X
D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D055785:Gene Knockdown Techniques; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D010539:Permeability; D050199:Podocytes / Q000378:metabolism / Q000502:physiology*; D012710:Serum Albumin, Bovine / Q000378:metabolism
D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C404495:Angptl3 protein, mouse; D008565:Membrane Proteins; C039217:fluorescein isothiocyanate bovine serum albumin; C113267:nephrin; D012710:Serum Albumin, Bovine; D016650:Fluorescein-5-isothiocyanate