Table 1.
Summary of recent studies identifying molecules associated with activation of parietal epithelial cells (PECs)
| Signaling factor and treatment | Effect on PECs | Model | Study reference |
|---|---|---|---|
| mTORC1 inhibition | Increased proliferation Increased PEC density |
Mouse model of acute podocyte depletion Aging mice |
McNicholas et al. 2016 |
| mTORC1 inhibition or L-type neutral amino acid transporters inhibition | Cell necrosis Decreased crescent formation |
Rats with crescentic glomerulonephritis (CrGN); WKY/NCrj rats injected with anti-glomerular basement membrane | Kurayama et al. 2011 |
| Sestrin 2 reduction and increased mTOR activity (observation) Sestrin 2 inhibition in vitro |
Associated with increased apoptosis or proliferation (dependent on the disease model) Increased apoptosis (in vitro) |
Adriamycin and pruromycin nephropathy model in rat CrGN Conditionally immortalized mouse PEC cells |
Hamatani et al. 2014 |
| Reduced phosphorylated extracellular signal-regulated kinase 1 and 2 (p-ERK1/2) (observation) | PEC apoptosis | Mouse model of protein overload nephropathy Conditionally immortalized mouse PEC cells |
Chang et al. 2012 |
| Matrix metalloproteinase 9 increase and ERK activation (observation) | Possible increased migration and loss of adjacent podocytes | Zucker diabetic fatty rats Primary rat PECs |
Zhang et al. 2015 |
| Glucocorticoid receptor (GR) inhibition | Decreased PEC activation De novo expression of podocyte markers |
Mouse model of acute podocyte depletion | Zhang et al. 2013 |
| Cell specific GR inactivation and systemic GR activation and inhibition | Decreased proliferation and migration Decreased crescent formation |
Pax8-Cre/GRfl/fl mice with induced CrGN glomerulonephritis (NTN model) | Kuppe et al. 2016 |
| Migration inhibitory factor (MIF) and CD47 deficiency MIF stimulation in vitro |
Decreased PEC activation and proliferation Decreased crescent formation Induced PEC proliferation |
NTN model in: MIF-/- mice CD47-/- mice Primary murine PECs |
Djudjaj et al. 2016 |
| Notch1 inhibition Notch1 inhibition in vitro |
Reduced PEC proliferative lesions and reduced exspression of mesenchymal markers Decreased migration and mesenchymal transcript expression |
NEP25 mice model for cFSGS Immortalized murine PEC cell line |
Ueno et al. 2013 |
| Interferon-α stimulation in vitro | Cell-cycle arrest and inhibition of migration of PECs | Immortalized murine PEC cell line | Migliorini et al. 2013 |
| SSeCKS deficiency | Increased proliferation | NTN model in SSeCKS-/- mice | Burnworth et al. 2012 |
| Angiotensin II inhibition (via ACEi) | Decreased proliferation of PEC Less extracapillary lesions |
MWF rats (spontaneous glomerulopathy) | Benigni et al. 2011 |