EPA and DHA suppress AngII- and arachidonic acid-induced expression of profibrotic genes in human mesangial cells.
BACKGROUND
There is some evidence suggesting a close relationship between polyunsaturated fatty acids (PUFAs) and renal inflammation and fibrosis, which are crucial stages in chronic kidney disease.


METHODS
To verify the role of PUFAs in renal fibrosis processes, we investigated the effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) on the gene expression of TGFbeta, fibronectin (FN), connective tissue growth factor (CTGF) and type IV collagen (COLIV) in human mesangial cells, in the absence or presence of angiotensin II (AngII), using reverse transcriptase PCR.


RESULTS
The addition of AA to mesangial cell cultures induced a significant up-regulation of TGFbeta, FN, CTGF and COLIV expression, similar to that induced by AngII, while EPA and DHA had no stimulatory effects. The coincubation of cells with AngII and AA potentiated AngII-induced gene expression; on the contrary, the coexposure of cells to EPA or DHA suppressed the AngII- and AA-induced up-regulation of TGFbeta, FN, CTGF and COLIV.


CONCLUSIONS
We conclude that the PUFAs have different effects, dependent on their chemical structure, on the AngII-TGFbeta system, a major regulator of the renal fibrotic process. Our in vitro results may provide new therapeutic options toward interrupting the irreversible process of renal fibrosis and ameliorating chronic renal injury.
Priante
Giovanna
G
Nephrology Unit, Department of Medical and Surgical Sciences, University of Padova, Padova, Italy.
Musacchio
Estella
E
Valvason
Chiara
C
Baggio
Bruno
B
D000804:Angiotensin II / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005353:Fibronectins / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D024141:Collagen Type IV; D005353:Fibronectins; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid