title: Human renal stem/progenitor cells repair tubular epithelial cell injury through TLR2-driven inhibin-A and microvesicle-shuttled decorin.
abstract: Acute kidney injury (AKI) is emerging as a worldwide public health problem. Recent studies have focused on the possibility of using human adult renal stem/progenitor cells (ARPCs) to improve the repair of AKI. Here we studied the influence of ARPCs on the healing of cisplatin-injured renal proximal tubular epithelial cells. Tubular, but not glomerular, ARPCs provided a protective effect promoting proliferation of surviving tubular cells and inhibiting cisplatin-induced apoptosis. The recovery effect was specific to tubular ARPCs, occurred only after damage sensing, and was completely cancelled by TLR2 blockade on tubular ARPCs. Moreover, tubular, but not glomerular, ARPCs were resistant to the apoptotic effect of cisplatin. Tubular ARPCs operate mainly through the engagement of TLR2, the secretion of inhibin-A protein, and microvesicle-shuttled decorin, inhibin-A, and cyclin D1 mRNAs. These factors worked synergistically and were essential to the repair process. The involvement of tubular ARPC-secreted inhibin-A and decorin mRNA in the pathophysiology of AKI was also confirmed in transplant patients affected by delayed graft function. Hence, identification of this TLR2-driven recovery mechanism may shed light on new therapeutic strategies to promote the recovery capacity of the kidney in acute tubular damage. Use of these components, derived from ARPCs, avoids injecting stem cells.
authors: Department of Emergency and Organ Transplantation, University of Bari, Valenzano (BA), Italy.
authors: Fabio
authors: F
authors: Sallustio
authors: Vincenzo
authors: V
authors: Costantino
authors: Sharon N
authors: SN
authors: Cox
authors: Antonia
authors: A
authors: Loverre
authors: Chiara
authors: C
authors: Divella
authors: Marco
authors: M
authors: Rizzi
authors: Francesco P
authors: FP
authors: Schena
mesh_terms: D058186:Acute Kidney Injury / Q000628:therapy*; D000328:Adult; D017209:Apoptosis; D049109:Cell Proliferation; D002469:Cell Separation; D002945:Cisplatin / Q000633:toxicity; D019938:Cyclin D1 / Q000502:physiology; D058575:Decorin / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007265:Inhibins / Q000032:analysis / Q000502:physiology*; D007668:Kidney / Q000166:cytology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D012038:Regeneration; D033581:Stem Cell Transplantation; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C530104:CCND1 protein, human; C546878:DCN protein, human; D058575:Decorin; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C422362:inhibin A; D019938:Cyclin D1; D007265:Inhibins; D002945:Cisplatin