miR-1915 and miR-1225-5p regulate the expression of CD133, PAX2 and TLR2 in adult renal progenitor cells

PLoS One. 2013 Jul 8;8(7):e68296. doi: 10.1371/journal.pone.0068296. Print 2013.

Abstract

Adult renal progenitor cells (ARPCs) were recently identified in the cortex of the renal parenchyma and it was demonstrated that they were positive for PAX2, CD133, CD24 and exhibited multipotent differentiation ability. Recent studies on stem cells indicated that microRNAs (miRNAs), a class of noncoding small RNAs that participate in the regulation of gene expression, may play a key role in stem cell self-renewal and differentiation. Distinct sets of miRNAs are specifically expressed in pluripotent stem cells but not in adult tissues, suggesting a role for miRNAs in stem cell self-renewal. We compared miRNA expression profiles of ARPCs with that of mesenchymal stem cells (MSCs) and renal proximal tubular cells (RPTECs) finding distinct sets of miRNAs that were specifically expressed in ARPCs. In particular, miR-1915 and miR-1225-5p regulated the expression of important markers of renal progenitors, such as CD133 and PAX2, and important genes involved in the repair mechanisms of ARPCs, such as TLR2. We demonstrated that the expression of both the renal stem cell markers CD133 and PAX2 depends on lower miR-1915 levels and that the increase of miR-1915 levels improved capacity of ARPCs to differentiate into adipocyte-like and epithelial-like cells. Finally, we found that the low levels of miR-1225-5p were responsible for high TLR2 expression in ARPCs. Therefore, together, miR-1915 and miR-1225-5p seem to regulate important traits of renal progenitors: the stemness and the repair capacity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adult
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • Cell Separation
  • Cluster Analysis
  • Computer Simulation
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Humans
  • Kidney Glomerulus / cytology
  • Kidney Tubules, Proximal / cytology
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • PAX2 Transcription Factor / genetics*
  • PAX2 Transcription Factor / metabolism
  • Peptides / genetics*
  • Peptides / metabolism
  • Principal Component Analysis
  • Reproducibility of Results
  • Stem Cells / metabolism*
  • Toll-Like Receptor 2 / genetics*
  • Toll-Like Receptor 2 / metabolism
  • Up-Regulation / genetics

Substances

  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • MIRN1225 microRNA, human
  • MIRN1915 microRNA, human
  • MicroRNAs
  • PAX2 Transcription Factor
  • PAX2 protein, human
  • PROM1 protein, human
  • Peptides
  • TLR2 protein, human
  • Toll-Like Receptor 2

Grant support

This study was supported by a grant from Ministero dell'Istruzione, dell'Università e della Ricerca (MiUR) (PRIN 2008M9WSJX; PON-REC ONEV 134/2011; FIRB RBAP11B2SX) and “Regione Puglia” (Progetto strategico 44/09 BISIMANE; Progetto strategico 2006 PS 144/06). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.