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Unveiling Angiotensin II and Losartan-Induced Gene Regulatory Networks Using Human Urine-Derived Podocytes
Chantelle Thimm1, Lars Erichsen1, Wasco Wruck1
1Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.
International Journal of Molecular Sciences
|July 14, 2023
Summary
Researchers differentiated urine-derived renal progenitor cells into podocytes. These cells model how angiotensin II and losartan affect the renin-angiotensin-aldosterone system (RAAS), aiding kidney disease research.
Area of Science:
- Nephrology
- Regenerative Medicine
- Molecular Biology
Background:
- Podocytes are crucial for kidney filtration; their injury causes renal diseases.
- Hypertension involves the renin-angiotensin-aldosterone system (RAAS), with angiotensin II (ANG II) mediating podocyte apoptosis.
- Losartan, an angiotensin-II-type I receptor (AGTR1) blocker, is used to treat hypertension by modulating RAAS.
Purpose of the Study:
- To differentiate SIX2-positive urine-derived renal progenitor cells (UdRPCs) into mature podocytes.
- To investigate the effects of ANG II and losartan on RAAS signaling in differentiated podocytes.
- To analyze gene expression changes induced by losartan and ANG II co-stimulation.
Main Methods:
- Differentiation of UdRPCs and UM51-hTERT cells into mature podocytes.
- Stimulation of differentiated podocytes with ANG II and losartan.
- Analysis of angiotensin-II receptor expression (AGTR1 and AGTR2).
- Transcriptome analysis to identify differentially expressed genes.
Main Results:
- Differentiated podocytes exhibited ANG II-dependent RAAS activation, upregulating AGTR1 and downregulating AGTR2.
- Losartan treatment counteracted ANG II effects, favoring AGTR2 over AGTR1.
- Transcriptome analysis identified key genes and pathways affected by losartan and co-stimulation, including those related to vascular function, DNA methylation, and cell differentiation.
Conclusions:
- UdRPC-derived podocytes serve as a valuable model for studying RAAS pathway activation and modulation in kidney disease.
- This model facilitates research into nephrotoxicity and potential therapeutic strategies targeting the RAAS.
- The findings provide insights into the molecular mechanisms underlying losartan's effects on podocytes.
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