Spatial and temporally restricted expression of chemokines and chemokine receptors in the developing human kidney.

Abstract

The directed migration of cells, cell-cell adhesion, and the control of proliferation are key events during metanephric development. The chemokines are a family of proteins that selectively control aspects of cell migration, activation, proliferation, and adhesion. The expression of a series of chemokines and chemokine receptors during human renal development was investigated by using immunohistochemical analyses and real-time reverse transcription-PCR assays of defined laser-microdissected metanephric structures. The results demonstrate that mononuclear cell-like cells within the nephrogenic blastema focally express interferon-inducible protein-10/CXCL10, a ligand for CXCR3. Mononuclear-like cells dispersed through the developing organ express CX(3)CR1. Expression of CXCR4, the receptor for stromal cell-derived factor-1/CXCL12, is also limited to stromal CD34-positive cells. In contrast, the expression of stromal cell-derived factor-1/CXCL12, fractalkine, and CXCR3 is first observed in the comma- or S-shaped body stage. The intensity of this expression becomes stronger in the capillary loop stage, and expression is mainly observed in the mesangial stalk and endothelial cells of the glomeruli. These proteins may play modulatory roles in kidney development. Because genes that are expressed during ontogeny often play a role in tissue regeneration, these embryonal chemokine/chemokine receptor patterns may be important in renal injury and repair.