Table 5.
Kidney diseases associated with genetic intervention of autophagy in mice.
| Setting | Genetic intervention | Effects on disease phenotype | Ref. |
|---|---|---|---|
| Acute kidney injury | Distal and proximal TEC‐specific deletion of Atg5 | Impaired kidney function and increased sensitivity to ischemic injury, linked to accumulation of damaged mitochondria | Liu et al (2012) |
| Acute kidney injury | Proximal TEC‐specific deletion of Atg5 | Exacerbated nephropathy induced by oxalate crystals | Nakamura et al (2020) |
| Acute kidney injury | Proximal TEC‐specific deletion of Rubcn | Increased sensitivity to ischemic injury, linked to increased fat efflux from cells to circulation, after autophagy activation | Matsuda et al (2020) |
| Acute kidney injury | Whole‐body deletion of Pink1 and/or Prkn | Increased sensitivity to ischemic injury linked to damaged mitochondria, ROS production, and inflammatory response, after mitophagy inhibition | Tang et al (2018) |
| Acute kidney injury | Proximal TEC‐specific deletion of Tfeb | Enhanced progression of kidney injury induced by oxalate crystals, linked to exacerbation of lysosomal damage. | Nakamura et al (2020) |
| Diabetic kidney disease | Podocyte‐specific deletion of Atg5 | Accelerated diabetes‐induced podocytopathy with a leaky GFB and glomerulosclerosis | Lenoir et al (2015) |
| Diabetic kidney disease | Proximal TEC‐specific deletion of Atg7 | Exacerbated renal hypertrophy, tubular damage, fibrosis, inflammation, and albuminuria in diabetic mice | Lenoir et al (2015), Ma et al (2020) |
| Diabetic kidney disease | Whole‐body deletion of Sglt2 | Reduced glomerular hyperfiltration, linked to decreased accumulation of SQSTM1 in streptozotocin‐treated mice | Vallon et al (2013) |
| Diabetic kidney disease | Proximal TEC‐specific deletion of miR‐214 or Tp53 | Reduced renal hypertrophy and albuminuria, by preventing autophagy impairment in diabetic kidneys | Ma et al (2020) |
| Focal segmental glomerulosclerosis | Nephron‐specific deletion of Atg5 or Atg7 | Development of kidney dysfunction by 2 months and organ failure by 6 months | Kawakami et al (2015) |
| Focal segmental glomerulosclerosis | Podocyte‐specific deletion of Atg5 | Development of early glomerulopathy and proteinuria in aging mice, resulting in late‐onset glomerulosclerosis | Hartleben et al (2010) |
| Focal segmental glomerulosclerosis | Conditional podocyte‐specific deletion of Vps34 | Premature death, development of early‐onset proteinuria and glomerulosclerosis | Bechtel et al (2013) |
| Focal segmental glomerulosclerosis | Podocyte‐specific deletion of Ctsd | Development of late‐onset glomerulosclerosis and proteinuria in aging mice | Yamamoto‐Nonaka et al (2016) |
| Kidney fibrosis | Proximal TEC (S3 segment)‐specific deletion of Atg5 | Reduced tubular atrophy, senescence, and inflammation, linked to superior renal function 30 days after IRI | Baisantry et al (2016) |
| Kidney fibrosis | Conditional proximal TEC‐specific deletion of Atg7 | Reduced tubular atrophy, nephron loss, and macrophages infiltration, during UUO‐induced fibrosis | Livingston et al (2016) |
| Kidney fibrosis | Whole‐body deletion of Map1 lc3b | Exacerbated UUO‐induced fibrosis, linked to increased collagen deposition and TGF‐β production | Ding et al (2014) |
| Kidney fibrosis | Whole‐body allelic loss of Becn1 | Exacerbated UUO‐induced fibrosis, linked to increased collagen deposition and TGF‐β production | Ding et al (2014) |
| Kidney fibrosis | Conditional distal TEC‐specific deletion of Atg7 | Exacerbated UUO‐induced fibrosis, linked to accumulation of damaged mitochondria and TGF‐β production | Nam et al (2019) |
| Kidney fibrosis | Whole‐body deletion of Pink1 or Prkn | Exacerbated UUO‐induced fibrosis, linked to impaired macrophage mitochondrial homeostasis | Bhatia et al (2019) |
| Kidney fibrosis | Myeloid cell‐specific deletion of Mfn2 | Exaggerated kidney fibrosis after inhibition of macrophage mitophagy | Bhatia et al (2019) |
| Kidney fibrosis | Whole‐body αKlotho haploinsufficiency | Exacerbated renal fibrosis and accelerated CKD progression upon high phosphate diet following UNX | Shi et al (2016) |
| Kidney insufficiency | Conditional proximal TEC‐specific deletion of Vps34/PI3KC3 | Impaired autophagy flux, causing a Fanconi‐like syndrome and renal insufficiency | Grieco et al (2018) |
| Proteinuria | Podocyte‐specific deletion of Atg7 | Higher levels of proteinuria and ultrastructural changes following UNX | Oliva Trejo et al (2014) |
CKD, chronic kidney disease; IRI, ischemia‐reperfusion injury; GFB, glomerular filtration barrier; ROS, reactive oxygen species; TEC, tubular epithelial cell; UNX, unilateral nephrectomy; UUO, unilateral ureteric obstruction.