Albumin caused the increasing production of angiotensin II due to the dysregulation of ACE/ACE2 expression in HK2 cells.
BACKGROUND
Previous studies have proposed that albuminuria is involved in the activation of intrarenal renin angiotensin system (RAS), while its potential mechanism is still unclear. We investigated the influence of albumin on the expression of ACE/ACE2 and generation of Ang II in HK2 cells.


METHODS
The mRNA and protein expression of ACE and ACE2 was determined by RT-PCR and western blot respectively. Cellular localization of ACE and ACE2 was shown by laser scanning confocal microscope (LSCM). The concentration of Ang II in the supernatant was detected by radioimmunoassay (RIA).


RESULTS
Treatment of HK-2 cells to BSA led to a significant increasing expression of ACE mRNA in dose and time dependent manner. The overexpression of ACE protein induced by BSA was consistent with its mRNA expression. Meanwhile, the mRNA and protein expression of ACE2 upon the stimulation of BSA was significantly downregulated in dose and time dependent manner. BSA could significantly increase the production of Ang II in the supernatant (p<0.05). Captopril, however, attenuated the expression of ACE but increased expression of ACE2 induced by BSA.


CONCLUSIONS
These findings suggested a novel insight on the albuminuria induced activation of intrarenal RAS by upregulation of ACE and downregulation of ACE2.
Liu
Bi-Cheng
BC
Institute of Nephrology, Zhong Da Hospital, Southeast University, Nanjing, 210009, China. liubc64@yahoo.com.cn
Gao
Jun
J
Li
Qing
Q
Xu
Li-Min
LM
D000804:Angiotensin II / Q000096:biosynthesis* / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism*; D011507:Proteinuria / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D000804:Angiotensin II; D012710:Serum Albumin, Bovine; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2