| First Author | Monteith AJ | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 37 | Pages | eabj2101 |
| PubMed ID | 34516771 | Mgi Jnum | J:314197 |
| Mgi Id | MGI:6766219 | Doi | 10.1126/sciadv.abj2101 |
| Citation | Monteith AJ, et al. (2021) Neutrophil extracellular traps enhance macrophage killing of bacterial pathogens. Sci Adv 7(37):eabj2101 |
| abstractText | Podocyte loss triggering aberrant activation and proliferation of parietal epithelial cells (PECs) is a central pathogenic event in proliferative glomerulopathies. Podocyte-specific KrÃŒppel-like factor 4 (KLF4), a zinc-finger transcription factor, is essential for maintaining podocyte homeostasis and PEC quiescence. Using mice with podocyte-specific knockdown of Klf4, we conducted glomerular RNA-sequencing, tandem mass spectrometry, and single-nucleus RNA-sequencing to identify cell-specific transcriptional changes that trigger PEC activation due to podocyte loss. Integration with in silico chromatin immunoprecipitation identified key ligand-receptor interactions, such as fibronectin 1 (FN1)âαVβ6, between podocytes and PECs dependent on KLF4 and downstream signal transducer and activator of transcription 3 (STAT3) signaling. Knockdown of Itgb6 in PECs attenuated PEC activation. Additionally, podocyte-specific induction of human KLF4 or pharmacological inhibition of downstream STAT3 activation reduced FN1 and integrin β 6 (ITGB6) expression and mitigated podocyte loss and PEC activation in mice. Targeting podocyte-PEC crosstalk might be a critical therapeutic strategy in proliferative glomerulopathies. |
