TLR2 plays a role in the activation of human resident renal stem/progenitor cells.
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.
Nephrology Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Policlinico, Piazza G. Cesare No 11, 70124, Bari, Italy.
Fabio
F
Sallustio
Luc
L
De Benedictis
Giuseppe
G
Castellano
Gianluigi
G
Zaza
Antonia
A
Loverre
Vincenzo
V
Costantino
Giuseppe
G
Grandaliano
Francesco P
FP
Schena
D000071916:AC133 Antigen; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D051927:CD24 Antigen / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D002999:Clone Cells / Q000502:physiology; D003176:Complement C3 / Q000378:metabolism; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007678:Kidney Glomerulus / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000502:physiology*
D000071916:AC133 Antigen; D015703:Antigens, CD; C111835:CCL2 protein, human; D051927:CD24 Antigen; C497889:CD24 protein, human; D018932:Chemokine CCL2; D003176:Complement C3; D006023:Glycoproteins; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D010455:Peptides; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2