Rapamycin and dexamethasone during pregnancy prevent tuberous sclerosis complex–associated cystic kidney disease

Arginine depletion attenuates renal cystogenesis in tuberous sclerosis complex model

“… 32 We previously showed that these mice have a postnatal lethal phenotype with mTORC1 hyperactivation in PTCs throughout pregnancy and a cystic phenotype visible at E17.5. 15 Tsc1 fl/fl female mice were mated with Six2 Cre tg/+ Tsc1 fl/+ males to generate Six2 Cre tg/+ Tsc1 fl/fl pups with NPC-specific Tsc1 deletion (25% of offspring, herein Tsc1 KO). Pregnant Tsc1 fl/fl females were injected with vehicle or rapamycin, a potent and specific inhibitor of mTORC1, at E12.5, E14.5, and E16.5, as before.…”

“…Rapamycin or dexamethasone treatment during pregnancy alleviated cystic kidney disease by inhibiting the mTORC1 pathway and the inflammatory response. 15 Other mechanisms associated with TSC cyst development were also proposed. Tsc2 deletion accelerated extracellular vesicle (EV) production in the damaged cells with a distinct protein reservoir involved in diverse biological processes such as cellular proliferation, stress response, and metabolic pathways.…”

“…Indeed, PTCs obtained from TSC mouse kidneys are characterized by significant perturbation in expressions of genes associated with major metabolic pathways such as glucose metabolism, oxidative phosphorylation, the tricarboxylic acid (TCA) cycle, and lipid metabolism. 15 …”

Increasing mTORC1 Pathway Activity or Methionine Supplementation during Pregnancy Reverses the Negative Effect of Maternal Malnutrition on the Developing Kidney

“…An equal amount of protein extract was analyzed by SDS-PAGE as previously described using the antibodies as above, rabbit anti-pS6 ribosomal protein, and mouse anti-S6 ribosomal protein (2317; Cell Signaling), according to the manufacturer’s instructions. 40,41…”

“…An equal amount of protein extract was analyzed by SDS-PAGE as previously described using the antibodies as above, rabbit anti-pS6 ribosomal protein, and mouse anti-S6 ribosomal protein (2317; Cell Signaling), according to the manufacturer's instructions. 40,41 Biochemical Analyses For kidney function assessments, serum from the indicated mice in each group was collected and analyzed for serum urea using the QuantiChrom Urea assay kit (DIUR-100; Bio-Assay Systems). Serum levels of creatinine were determined by using the Cobas C-111 chemistry analyzer (Roche).…”