First Author | Motojima M | Year | 2017 |
Journal | Exp Cell Res | Volume | 352 |
Issue | 2 | Pages | 265-272 |
PubMed ID | 28223138 | Mgi Jnum | J:240396 |
Mgi Id | MGI:5883353 | Doi | 10.1016/j.yexcr.2017.02.016 |
Citation | Motojima M, et al. (2017) Foxc1 and Foxc2 are necessary to maintain glomerular podocytes. Exp Cell Res 352(2):265-272 |
abstractText | Foxc1 and Foxc2 (Foxc1/2) are transcription factors involved in many biological processes. In adult kidneys, expression of Foxc1/2 is confined to the glomerular epithelial cells, i.e., podocytes. To bypass embryonic lethality of Foxc1/2 null mice, mice ubiquitously expressing inducible-Cre (ROSA26-CreERT2) or mice expressing Cre in podocytes (Nephrin-Cre) were mated with floxed-Foxc1 and floxed-Foxc2 mice. The CreERT2 was activated in adult mice by administrations of tamoxifen. Eight weeks after tamoxifen treatment, ROSA26-CreERT2; Foxc1+/flox; Foxc2flox/flox mice developed microalbuminuria, while ROSA26-Cre ERT2; Foxc1flox/flox; Foxc2+/flox mice had no microalbuminuria. The kidneys of conditional-Foxc1/2 null mice showed proteinaceous casts, protein reabsorption droplets in tubules and huge vacuoles in podocytes, indicating severe podocyte injury and massive proteinuria. Comparison of gene expression profiles revealed that Foxc1/2 maintain expression of genes necessary for podocyte function such as podocin and Cxcl12. In addition, mice with an innate podocyte-specific deletion of Foxc1/2 by Nephrin-Cre develop similar podocyte injury. These results demonstrate dose-dependence of Foxc1/2 gene in maintaining the podocyte with a more critical role for Foxc2 than Foxc1 and a critical role of Foxc1/2 in regulating expression of genes that maintain podocyte integrity. |