Unknown

Dataset Information

0

CSF-1 signals directly to renal tubular epithelial cells to mediate repair in mice.


ABSTRACT: Tubular damage following ischemic renal injury is often reversible, and tubular epithelial cell (TEC) proliferation is a hallmark of tubular repair. Macrophages have been implicated in tissue repair, and CSF-1, the principal macrophage growth factor, is expressed by TECs. We therefore tested the hypothesis that CSF-1 is central to tubular repair using an acute renal injury and repair model, ischemia/reperfusion (I/R). Mice injected with CSF-1 following I/R exhibited hastened healing, as evidenced by decreased tubular pathology, reduced fibrosis, and improved renal function. Notably, CSF-1 treatment increased TEC proliferation and reduced TEC apoptosis. Moreover, administration of a CSF-1 receptor-specific (CSF-1R-specific) antibody after I/R increased tubular pathology and fibrosis, suppressed TEC proliferation, and heightened TEC apoptosis. To determine the contribution of macrophages to CSF-1-dependent renal repair, we assessed the effect of CSF-1 on I/R in mice in which CD11b+ cells were genetically ablated and determined that macrophages only partially accounted for CSF-1-dependent tubular repair. We found that TECs expressed the CSF-1R and that this receptor was upregulated and coexpressed with CSF-1 in TECs following renal injury in mice and humans. Furthermore, signaling via the CSF-1R stimulated proliferation and reduced apoptosis in human and mouse TECs. Taken together, these data suggest that CSF-1 mediates renal repair by both a macrophage-dependent mechanism and direct autocrine/paracrine action on TECs.

SUBMITTER: Menke J 

PROVIDER: S-EPMC2719924 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC5832874 | biostudies-other
2021-08-20 | MTBLS608 | MetaboLights
| S-EPMC8476913 | biostudies-literature
2022-02-17 | PXD029651 | Pride
| S-EPMC8599682 | biostudies-literature
| S-EPMC2716958 | biostudies-literature
| S-EPMC4108915 | biostudies-other
| S-EPMC6497644 | biostudies-literature
| S-EPMC5707188 | biostudies-literature
| S-EPMC8261442 | biostudies-literature