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Role of Extracellular Vesicles in TSC Renal Cystogenesis

Kamyar Zahedi1,2, Mackenzie Morgan1, Brenda Prieto1

  • 1Division of Nephrology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.

International Journal of Molecular Sciences
|April 17, 2025
PubMed

Insights

Extracellular vesicles (EVs) from Tuberous Sclerosis Complex (TSC) kidney cells with Tsc1 gene mutations inhibit proliferation. This suggests EVs play a role in TSC pathogenesis and cyst development.

Area of Science:

  • Cell Biology
  • Genetics
  • Biochemistry

Background:

  • Tuberous Sclerosis Complex (TSC) is a genetic disorder caused by mutations in TSC1 or TSC2 genes, affecting multiple organs.
  • TSC proteins regulate cell growth via the mechanistic target of rapamycin complex 1 (mTORC1) pathway.
  • Extracellular vesicles (EVs) mediate intercellular communication, but their role in TSC pathogenesis is unclear.

Purpose of the Study:

  • To investigate the role of EVs in TSC pathogenesis.
  • To determine if EVs from Tsc1-deficient cells affect the function and proliferation of normal cells.

Main Methods:

  • Isolation and characterization of EVs from wildtype and Tsc1 knockout (Tsc1KO) mouse kidneys using Western blotting, electron microscopy, and nanoparticle tracking.
  • RNA sequencing (RNA-seq) and proteomic analysis to identify EV cargo.
  • Assay of M-1 cell proliferation after exposure to EVs from Tsc1KO mice.

Main Results:

  • EVs isolated from Tsc1KO mice exhibited similar particle sizes and EV marker enrichment compared to wildtype.
  • Significant differences were observed in the RNA and protein content of EVs from Tsc1KO mice.
  • EVs derived from Tsc1KO mice demonstrated an inhibitory effect on M-1 cell proliferation.

Conclusions:

  • EVs carry distinct molecular cargo in the absence of functional Tsc1.
  • EVs from Tsc1-deficient cells can modulate the proliferation of normal cells, suggesting a role in TSC.
  • Further understanding of EV involvement in TSC cystogenesis may offer novel therapeutic strategies.
Keywords:
A-intercalated cellscollecting ductcystogenesisextracellular vesicleskidneyprincipal cellstuberous sclerosis complex

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