Table 2.
Transgenic murine models of altered senescence induction and their outcomes in the kidney.
| Reference | Renal model | Modulation of senescence | Renal Disease outcome | Effect of any Intervention |
|---|---|---|---|---|
| Baker et al. (2016) | Natural aging In INK-ATTAC mice |
INK-ATTAC +AP20187 or vehicle administration to deplete P16INK4A+ cells |
↑Glomerulosclerosis ↑ ß-gal positivity |
↓Glomerulosclerosis ↓ß-gal positivity |
| Baar et al. (2017) | Natural aging P16-3MR mice and fast aging Xpd TTD/TTD mice |
FOXO4-DRI agent causes p53 nuclear exclusion. Ganciclovir Rx to P16-3MR mice causes P16INK4A+ restricted cell death |
↑Serum Urea ↓Lmnb1 expression ↑SASP expression (both XpdTTD/TTD and aged P16-3MR) |
FOXO4-DRI or GCV to P16-3MR admin: ↓Serum Urea ↑Lmnb1 expression ↓SASP expression (both XpdTTD/TTD and aged P16-3MR) |
| Munoz-Espin et al. (2013) | Nephrogenesis | WT vs P21CIP1 KO mice with deficient growth arrest in nephrogenesis |
↓ ß-gal positivity in P21CIP1 KO mice utero. ↑Ki67 expression but ↑Apoptosis maintains development | Use of PI3K inhibitor augments developmental senescence in WT mice |
| Wolstein et al. (2010) | UUO | WT vs P16INK4A KO mice with impaired cell cycle arrest | UUO induces ß-gal positivity, apoptosis and collagen deposition in WT mice | ↓ ß-gal positivity ↓Apoptosis ↑Collagen, ↑proliferation after UUO in P16INK4A KO |
| Megyesi et al. (2001) | Renal IRI | WT vs P21CIP1 KO mice with impaired cell cycle arrest | WT mice show tubular injury and raised blood urea levels after IRI | ↑proliferation ↓Renal function ↑Mortality in P21CIP1 KO |
| Megyesi et al. (2015) | Renal UUO and IRI | WT vs P21CIP1 KO vs P21CIP1 KO+KAP2-driven P21CIP1 | WT mice show renal fibrosis after both UUO and IRI | UUO: ↓fibrosis in P21CIP1 KO vs WT, ↑fibrosis in P21CIP1 KO kidneys with KAP2 promotor driven P21CIP1 vs P21CIP1 KO. IRI: ↑TGFß1 in P21CIP1 KO kidneys with KAP2 promotor driven P21CIP1 vs P21CIP1 KO. |
| Lee et al. (2012) | Renal IRI | WT vs P16INK4A/p19ARF Double KO mice with impaired cell cycle arrest | WT mice show marked P16INK4A and p19ARF induction 28d after IRI, with apotosis and reduced tubular density | P16INK4A and p19ARF deficient mice show improved epithelial and microvascular repair, with increased myeloid cell recruitment |
|
Al-Douahji et al. (1999) Wolf et al. (2005) |
Diabetic Nephropathy | WT vs P21CIP1 KO WT vs p27KIP1 KO |
WT mice develop albuminuria and glomerular hypertrophy | Both p27KIP1 KO and P21CIP1KO mice were protected from proteinuria and glomerular expansion |
| Braun et al. (2012) | Renal Transplant | P16INK4A KO mice with impaired cell cycle arrest | WT mice develop interstitial fibrosis and tubular atrophy | P16INK4A KO mice develop less atrophy and fibrosis after Tx |
In each case ↑ ↓ markers were used to indicate that the p value was less than 0.05.