. Author manuscript; available in PMC: 2022 Jul 1.

Published in final edited form as: Kidney Int. 2021 Apr 6;100(1):67–78. doi: 10.1016/j.kint.2021.03.024

Table 1 |.

Cell cycle dysregulation in RTECs and podocytes in kidney injury and disease

Cell cycle regulation/impairment	Mediators	Results	References
RTECs in AKI-CKD
G1/S transition delay	↑p53/p21 (and p27) and ↓CDK2/cyclin E activity	Improved RTEC recovery after AKI	46–48
G1/S transition delay	Transient CDK4/6 inhibition	Improved RTEC recovery after AKI	49, 50
G2/M checkpoint arrest	Cyclin → ↑p53/p21	SASP, TASCC formation, and fibrosis	6, 7
G2/M checkpoint arrest	TGF-β → ↑p21	Tubular damage, EMT, fibrosis	60, 61
Endocycling (Pax8⁺ RTECs)	Not identified	Polyploidy and hypertrophy	89
PKD (ADPKD)
Unchecked cell cycle progression	Loss of PC1 → ↓p53/p21	RTEC hyperproliferation	97, 172, 173
Unchecked cell cycle progression	Loss of PC1 → ↑Cux1, ↑Pax2		108, 111, 112 86, 87, 114
Premature G1/S transition	Loss of PC1 → ↓STAT1 activation → ↓Yp21	Cell cycle progression and hyperproliferation	97
	Loss of PC1 → ↑cyclin A		98, 99
	Loss of PC2 → ↑Id2 nuclear translocation and gene expression		100
Cytokinesis defects	Loss of PC1	Centrosomal amplification, MC	131, 141
Cytokinesis defects		Mitotic slippage/endomitosis, aberrant ploidy
RTECs in HIVAN
G2/M checkpoint arrest	Vpr → DNA damage response (ATM/ATR)	Caspase-mediated cell death	160, 161, 171
Cytokinesis defects	Vpr→ FAT10	Centrosome amplification, MC	162–166, 171
Cytokinesis defects	Vpr → DNA-PK	Mitotic slippage/endomitosis, aberrant ploidy

ADPKD, autosomal dominant polycystic kidney disease; AKI, acute kidney injury; ATM, Ataxia telangiectasia mutated; ATR, ATM and RAD3-related; CDK, cyclin-dependent kinase; CKD, chronic kidney disease; Cux, Cut-like homeobox; DNA-PK, DNA-dependent protein kinase; EMT, epithelial-to-mesenchymal transition; FAT10, HLA-F–adjacent transcript 10; HIVAN, HIV-associated nephropathy; MC, mitotic catastrophe; Pax, paired box; PC1, polycystin-1; PC2, polycystin-2; PKD, polycystic kidney disease; RTEC, renal tubular epithelial cell; SASP, senescence-associated secretory phenotype; STAT, signal transducers and activators of transcription; TASCC, target of rapamycin–autophagy spatial coupling compartment; TGF-β, transforming growth factor-β; Vpr, Viral Protein R.