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.

• Authors: Julia Menke, Yasunori Iwata, Whitney A Rabacal, Ranu Basu, Yee G Yeung, Benjamin D Humphreys, Takashi Wada, Andreas Schwarting, E Richard Stanley, Vicki R Kelley
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 119 Issue 8 Pg. 2330-42 (Aug 2009) ISSN: 1558-8238 [Electronic] United States
• PMID: 19587445 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Macrophage Colony-Stimulating Factor
• Receptor, Macrophage Colony-Stimulating Factor

Topics

• Animals
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Epithelial Cells (physiology)
• Fibrosis
• Humans
• Kidney Tubules (pathology, physiology)
• Macrophage Colony-Stimulating Factor (genetics, physiology)
• Macrophages (physiology)
• Mice
• Mice, Inbred C3H
• Receptor, Macrophage Colony-Stimulating Factor (genetics)
• Regeneration
• Reperfusion Injury (pathology, physiopathology)