Transforming growth factor-β activated long non-coding RNA ATB plays an important role in acute rejection of renal allografts and may impacts the postoperative pharmaceutical immunosuppression therapy

Nephrology (Carlton). 2017 Oct;22(10):796-803. doi: 10.1111/nep.12851.

Abstract

Aim: Long noncoding RNAs (lncRNAs) are novel intracellular noncoding ribonucleotides regulating the genome and proteome. The lncRNA activated by transforming growth factor β (TGF-β) (lncRNA-ATB) was discovered as a prognostic factor in hepatocellular carcinoma, gastric cancer, and colorectal cancer. However, little is known about the role of lncRNA-ATB in renal transplantation. This study aimed to assess lncRNA-ATB expression in renal transplant patients with acute kidney injury and explore its role in postoperative pharmaceutical immunosuppression therapy.

Methods: We detected lncRNA-ATB expression in the kidney biopsies of a cohort of 72 patients with renal allograft rejection and 36 control transplant patients. lncRNA-ATB were overexpressed from lentiviral vectors in renal cells.

Results: We found that lncRNA-ATB was remarkably upregulated in patients with acute rejection compared with controls. Meanwhile, lncRNA-ATB could influence the kidney cell phenotypes and impact the nephrotoxicity of immunosuppressive drug.

Conclusion: In conclusion, lncRNA-ATB are strongly altered in patients with acute rejection and may serve as a novel biomarker of acute kidney rejection, identifying patients with acute rejection and predicting loss of kidney function.

Keywords: acute rejection; apoptosis; calcineurin inhibitors; cell proliferation; lncRNA.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / genetics
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Adolescent
  • Adult
  • Aged
  • Allografts
  • Apoptosis / drug effects
  • Calcineurin Inhibitors / adverse effects*
  • Case-Control Studies
  • Cell Proliferation / drug effects
  • Cyclosporine / adverse effects*
  • Dose-Response Relationship, Drug
  • Female
  • Graft Rejection / genetics
  • Graft Rejection / metabolism
  • Graft Rejection / pathology
  • Graft Rejection / prevention & control*
  • HEK293 Cells
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Inhibitory Concentration 50
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Transplantation / adverse effects*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Treatment Outcome
  • Up-Regulation
  • Young Adult

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • MIRN200 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA ATB, human
  • Cyclosporine