[Show abstract][Hide abstract] ABSTRACT: In the past few years, adult renal progenitor/stem cells (ARPCs) have been identified in human kidneys, and particularly in Bowman's capsule and proximal tubules. They may play an important role in the kidney regenerative processes and might prospectively be the ideal cell type for the treatment of both acute and chronic renal injury. In this study, microarray analysis identified 6 gene clusters that discriminated normal human glomerular and tubular ARPCs from renal proximal tubular epithelial cells and mesenchymal stem cells. The top-scored pathway in the ARPC gene expression profile contained growth factor receptors and immune system-related genes, including toll-like receptor 2 (TLR2). Stimulation of TLR2 by ligands that mime inflammatory mediators or damage associated molecular pattern molecules induced secretion of elevated amounts of monocyte chemoattractant protein-1 (MCP-1), IL-6, IL-8, and C3 via NF-kappaB activation. TLR2 stimulation also increased the ARPC proliferation rate, suggesting a role for TLR2 in ARPC activation via autocrine signaling. Moreover, TLR2 stimulation improved ARPC differentiation into renal epithelial cells and was responsible of ARPC branching morphogenesis and tubule-like structures formation. For the first time, this study provides a genomic characterization of renal multipotent progenitor cells and shows that TLR2 found on ARPCs might be responsible for their activation in the kidney, orchestrating the activation of crucial signaling networks necessary for renal repair.