TABLE 4.
Modulators of renal cilia length.
Cilia length | Cell type | Mechanism or cellular effect | References | |
In vitro | ||||
↓ intracellular Ca2+ | ↑ | IMCD, MEK, BME | Increased anterograde IFT speed | Besschetnova et al., 2010 |
↑ intracellular cAMP | ↑ | IMCD, MEK, BME | Activated PKA; increased anterograde IFT speed | Besschetnova et al., 2010 |
Fluid flow | ↓ | IMCD, MEK, BME | ↓ cAMP; decreased cAMP and cilia length response abolished by Pkd1 and Pkd2 kd or mutation | Besschetnova et al., 2010 |
H2O2 (reactive oxygen species) | Deciliation | MDCK | Kim et al., 2013 | |
Dopamine | ↑ | LLC-PK1 | Increased cilia length increases intracellular Ca2+ response to fluid shear stress | Upadhyay et al., 2014 |
Cobalt chloride (hypoxia) | ↑ | MDCK | Increased HIF1-alpha | Verghese et al., 2011 |
aldosterone | ↑ | mCCD | Reduced degradation of IFT88 | Komarynets et al., 2020 |
In vivo | ||||
Pkd1RC/RC; Pkd1 ko or Pkd2 ko; Pkd1RC/RC:Pkhd1 ko | ↑ | Collecting duct; cyst-lining renal epithelia | Hopp et al., 2012; Liu et al., 2018; Olson et al., 2019 | |
Nek8jck/jck mutant | ↑ | Cyst lining renal epithelia | Smith et al., 2006 | |
Ischemia | ↓ 1 day after; ↑ 8 days after | Bowman’s capsule parietal epithelium, proximal tubule, collecting duct | Deciliation | Verghese et al., 2008; Kim et al., 2013 |
RBPj ko (Notch signaling downregulation) | ↑ | Cystic renal epithelia of developing kidney | Increased Akap12, a scaffolding protein that interacts with PKA, cyclins, and protein kinase C | Mukherjee et al., 2020 |
Hypoxia (chronic renal injury) | ↑ | Fetal ovine renal epithelia | Increased cilia length increased intracellular Ca2+ response to fluid shear stress | Shamloo et al., 2017 |
Mineralocorticoid receptor ko | ↓ | Distal nephron | Inability to respond to aldosterone | Komarynets et al., 2020 |
IMCD, mouse inner medullary collecting duct cells; MEK, mouse embryonic kidney cells; BME, bone mesenchymal cells; MDCK, Madin–Darby Canine Kidney cells; LLC-PK1, Lilly Laboratories Cell-Porcine Kidney 1 cells; mCCD, murine cortical collecting duct cells.