
Given the crucial roles of the intrarenal renin-angiotensin system and angiotensin II in the progression of kidney development and injury, we investigated expression of RAS components and effects of Ang II on cell differentiation in human kidney organoids. Ang II type 1 receptor was strongly expressed in the early phase of organoid development , whereas Ang II type 2 receptor expression levels peaked on day 5. Ang II-E was observed to decrease levels of marker genes for renal tubules and proximal tubules, and the downregulation of renal tubules was inhibited by an AT1R antagonist. In contrast, Ang II-M increased levels of markers for podocytes, ureteric tip, and nephrogenic mesenchyme, and an AT2R blocker attenuated the Ang II-M-induced augmentation of podocyte formation. The findings demonstrate RAS expression and Ang II exertion of biphasic effects on cell differentiation through distinct mediatory roles of AT1R and AT2R, providing a novel strategy to establish and further characterize the developmental potential of hiPSC-derived kidney organoids.
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