%0 Generic %A R.A., Melnyk %A J., Tam %A Y., Boie %A B.P., Kennedy %A M.D., Percival %D 2009 %T Supplementary Material for: Renin and Prorenin Activate Pathways Implicated in Organ Damage in Human Mesangial Cells Independent of Angiotensin II Production %U https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Renin_and_Prorenin_Activate_Pathways_Implicated_in_Organ_Damage_in_Human_Mesangial_Cells_Independent_of_Angiotensin_II_Production/5120725 %R 10.6084/m9.figshare.5120725.v1 %2 https://ndownloader.figshare.com/files/8705029 %2 https://ndownloader.figshare.com/files/8705032 %K Renin-angiotensin system %K Angiotensin II %K Renal diseases %K Renin %K Prorenin %K Transforming growth factor-β %X Background: The mechanism by which an activated renin-angiotensin system (RAS) leads to the development of renal diseases, such as fibrosis, is only partially explained by the downstream effects of angiotensin II. The discovery of a receptor that binds renin and prorenin, and the consequent production of profibrotic molecules, revealed a novel axis within the RAS pathway that may contribute to the pathogenesis of organ damage in patients with elevated renin and/or prorenin levels. Methods: To better understand the genes and networks underlying the receptor-mediated effects of renin and prorenin, a gene expression profiling study was performed on human mesangial cells in the presence of angiotensin-II-blocking agents. Results: Renin and prorenin induce highly overlapping gene expression signatures that are dependent, only in part, on the presence of the (pro)renin receptor. We found that 2 distinct pathways were activated by renin and prorenin: a TGFβ-dependent pathway and a TGFβ-independent pathway. Bioinformatic analysis was used to show that both pathways are highly enriched with genes implicated in fibrosis, hypertrophy and atherosclerosis. Conclusions: This study suggests that both renin and inactive prorenin are capable of inducing genetic programs that could contribute to end-organ damage and atherogenesis, through receptor-mediated angiotensin-independent mechanisms. %I Karger Publishers