Inhibin-A and Decorin Secreted by Human Adult Renal Stem/Progenitor Cells Through the TLR2 Engagement Induce Renal Tubular Cell Regeneration

Sci Rep. 2017 Aug 15;7(1):8225. doi: 10.1038/s41598-017-08474-0.

Abstract

Acute kidney injury (AKI) is a public health problem worldwide. Several therapeutic strategies have been made to accelerate recovery and improve renal survival. Recent studies have shown that human adult renal progenitor cells (ARPCs) participate in kidney repair processes, and may be used as a possible treatment to promote regeneration in acute kidney injury. Here, we show that human tubular ARPCs (tARPCs) protect physically injured or chemically damaged renal proximal tubular epithelial cells (RPTECs) by preventing cisplatin-induced apoptosis and enhancing proliferation of survived cells. tARPCs without toll-like receptor 2 (TLR2) expression or TLR2 blocking completely abrogated this regenerative effect. Only tARPCs, and not glomerular ARPCs, were able to induce tubular cell regeneration process and it occurred only after damage detection. Moreover, we have found that ARPCs secreted inhibin-A and decorin following the RPTEC damage and that these secreted factors were directly involved in cell regeneration process. Polysaccharide synthetic vesicles containing these molecules were constructed and co-cultured with cisplatin damaged RPTECs. These synthetic vesicles were not only incorporated into the cells, but they were also able to induce a substantial increase in cell number and viability. The findings of this study increase the knowledge of renal repair processes and may be the first step in the development of new specific therapeutic strategies for renal repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / metabolism
  • Adult
  • Adult Stem Cells / drug effects
  • Adult Stem Cells / metabolism*
  • Apoptosis / drug effects
  • Biomarkers
  • Cell Differentiation
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cisplatin / pharmacology
  • Decorin / biosynthesis*
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Humans
  • Inhibins / biosynthesis*
  • Kidney Tubules / metabolism*
  • Regeneration*
  • Toll-Like Receptor 2 / metabolism*

Substances

  • Biomarkers
  • Decorin
  • Toll-Like Receptor 2
  • inhibin A
  • Inhibins
  • Cisplatin