Aldosterone-induced inflammatory response of mesangial cells via angiotension II receptors.
BACKGROUND
In this study, we investigated whether AngII receptors (AT1a and AT2) contributed to the development of the aldosterone-induced inflammatory response of rat mesangial cells (RMCs).


METHODS
RMCs were isolated from the glomeruli of normal or diabetic rats which were produced by injection of streptozotocin, and cultured in high-glucose media. In order to evaluate the effects of aldosterone, the expression of AT1a, AT2, NF-κB and MCP-1 was detected. In addition, in order to evaluate the role of Ang II receptors, AT1a and AT2 genes were blocked and the expression of NF-κB and MCP-1 was detected. Moreover, for assessing the relationship between NF-κB and MCP-1, the NF-κB gene was blocked and MCP-1 expression was detected.


RESULTS
Aldosterone significantly increased AT1a, AT2, NF-κB and MCP-1 levels in RMCs in a dose-dependent manner, whereas eplerenone (EPI), a selective aldosterone antagonist, partly inhibited the effects of aldosterone. When AT1a and AT2 genes were blocked, the expression of NF-κB and MCP-1 was greatly inhibited. Moreover, when the NF-κB gene was silenced, the expression of MCP-1 was reduced.


CONCLUSIONS
We demonstrated that aldosterone induced an inflammatory response in RMCs cultured in high-glucose media via the AT1a and AT2 pathways.
Department of Nephropathy and Hemodialysis, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Jianbing
J
Hao
Department of Nephropathy and Hemodialysis, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Liansheng
L
Ren
Department of Nephropathy and Hemodialysis, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Lei
L
Zhang
Department of Nephropathy and Hemodialysis, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Deyang
D
Kong
Department of Nephropathy and Hemodialysis, The First Affiliated Hospital of Harbin Medical University, Harbin, China hao_lirong@163.com.
Lirong
L
Hao
D000450:Aldosterone / Q000009:adverse effects*; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000473:pathology; D055785:Gene Knockdown Techniques; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D003907:Dexamethasone
AT1a; AT2; Aldosterone; MCP-1; NF-κB; inflammatory response