Deciphering the Impact of RAC1-SPTAN1 in ARPKD Cystogenesis Using Multifaceted Models - PubMed
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- #ARPKD
- #cystogenesis
- #RAC1-SPTAN1
- ARPKD leads to severe renal cysts and kidney dysfunction with no approved treatments.
- Pkhd1-/- mice lack cystic phenotypes, necessitating better human disease models.
- Kidney organoid-on-chip models mimic distal-nephron cysts in ARPKD patients.
- RAC1/c-FOS identified as potential therapeutic targets in ARPKD.
- Reduced SPTAN1 levels regulate RAC1 activation and cystic pathology.
- SPTAN1-mutant models show distal-nephron cysts and elevated RAC1/c-FOS expression.
- Altered calcium signaling and increased intracellular calcium observed in cystic cells.
- SLC8A1, a sodium/calcium exchanger, marks cystic epithelia in ARPKD kidneys.
- CRISPR activation of SPTAN1 in PKHD1-/- organoids alleviates cystic phenotypes.
- SPTAN1 is central to ARPKD pathogenesis; epigenome editing shows therapeutic potential.