Crosstalk between mesangial and endothelial cells: angiotensin II down-regulates endothelin-converting enzyme 1.
OBJECTIVE
Since mesangial and endothelial cells interact in the kidney, the present experiments were designed to analyze the ability of human mesangial cells (HMC) to modulate endothelin-1 (ET-1) synthesis by human umbilical vein endothelial cells (HuVEC).


RESULTS
The supernatants of HuVEC/HMC contained significantly lower amounts of ET-1 than those of HuVEC alone. This effect was not due to a decreased prepro-ET-1 mRNA expression and was only partially the consequence of HMC-dependent ET-1 degradation. Therefore, we tested the influence of the coculture on endothelin-converting enzyme-1 (ECE-1), and found a significant reduction of its mRNA and protein levels as well as a decreased activity in HuVEC/HMC as compared to HuVEC alone. Using a pharmacological blockade approach (sulotrobam, BN52021, losartan or catalase), losartan was shown to completely abolish down-regulation of ECE-1 observed in HuVEC/HMC. Angiotensin II (AII) induced a dose and time-dependent inhibition of ECE-1 expression in HuVEC.


CONCLUSIONS
These results support the importance of cross-talk among different cell types in the regulation of vascular or renal function. ET-1, and particularly ECE-1, might constitute a target in this regulation. In addition, locally synthesized AII could be one of the mediators involved in the down-regulation of ECE-1.
López-Ongil
Susana
S
Research Unit, Príncipe de Asturias Hospìtal, Madrid, Spain. slopez.hupa@salud.madrid.org
Díez-Marqués
M-Luisa
ML
Griera
Mercedes
M
Rodríguez-Puyol
Manuel
M
Rodríguez-Puyol
Diego
D
D000804:Angiotensin II / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D019332:Endothelin-1 / Q000032:analysis / Q000276:immunology; D000072396:Endothelin-Converting Enzymes; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology
D019332:Endothelin-1; D012333:RNA, Messenger; D000804:Angiotensin II; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes