Table 1.

Hippo pathway modulators of kidney disease

Hippo Mediator	In Vitro Data	Mouse Model Phenotype	Human Kidney Disease	Reference(s)
KIBRA	1. KIBRA silencing impairs human podocyte polarity;	?	?	14, 66
	2. KIBRA overexpression promotes podocyte apoptosis.
Mst	?	?	?
Lats	1. LATS promotes YAP phosphorylation in podocytes.	?	?	66
	2. High glucose induces LATS phosphorylation in proximal tubular epithelial cells.
YAP	1. Promotes podocyte survival.	1. Constitutive YAP KO → embryonic lethal.	1. FSGS: reduced podocyte YAP.	5, 9, 48, 49, 56, 57, 63
	2. Proximal tubule epithelial cells exposed to high glucose → increased YAP expression.	2. Cap mesenchyme YAP deletion → Death at 48 h postbirth, hypoplastic kidneys, empty bladder, dramatic reduction in detectable glomeruli and proximal tubules.	2. ADPKD and ARPKD: nuclear YAP.
	3. Rat fibroblasts grown of stiff matrix → increased nuclear YAP/TAZ.	3. Nephric duct YAP deletion → death within 24 h; hydronephrotic kidneys with blind-ending megaureters at birth.	3. Renal carcinoma (clear cell, papillary, renal mixed epithelial and stromal): nuclear YAP.
		4. Podocyte-specific YAP deletion → FSGS.
		5. Streptozotocin-induced (type 1) and db/db diabetic models: YAP expression and phosphorylation increased.
TAZ	Rat fibroblasts grown of stiff matrix → increased nuclear YAP/TAZ.	1. Cap mesenchyme TAZ deletion → cystic cortical tubules.	?	9, 48, 49, 63
		2. Nephric duct deletion → normal development but double YAP/TAZ deletion in nephric duct → no ureters at E18.5.
		3. Constitutive TAZ null mice → cystic kidney disease.
		4. Streptozotocin-induced (type 1) and db/db diabetic models: TAZ expression decreased.

KO, knockout; FSGS, focal segmented glomerulosclerosis; ADPKD, autosomal dominant polycystic kidney disease; ARPKD, autosomal recessive polycystic kidney disease.