Integrative analyses of circulating small rnas and kidney graft transcriptome in transplant glomerulopathy

Canan Kuscu, Manjari Kiran, Akram Mohammed, Cem Kuscu, Sarthak Satpathy, Aaron Wolen, Elissa Bardhi, Amandeep Bajwa, James D. Eason, Daniel Maluf, Valeria Mas, Enver Akalin

Research output: Contribution to journalArticlepeer-review

Abstract

Transplant glomerulopathy develops through multiple mechanisms, including donor-specific antibodies, T cells and innate immunity. This study investigates circulating small RNA profiles in serum samples of kidney transplant recipients with biopsy-proven transplant glomeru-lopathy. Among total small RNA population, miRNAs were the most abundant species in the serum of kidney transplant patients. In addition, fragments arising from mature tRNA and rRNA were detected. Most of the tRNA fragments were generated from 5 ends of mature tRNA and mainly from two parental tRNAs: tRNA-Gly and tRNA-Glu. Moreover, transplant patients with transplant glomerulopathy displayed a novel tRNA fragments signature. Gene expression analysis from al-lograft tissues demonstrated changes in canonical pathways related to immune activation such as iCos-iCosL signaling pathway in T helper cells, Th1 and Th2 activation pathway, and dendritic cell maturation. mRNA targets of down-regulated miRNAs such as miR-1224-5p, miR-4508, miR-320, miR-378a from serum were globally upregulated in tissue. Integration of serum miRNA profiles with tissue gene expression showed that changes in serum miRNAs support the role of T-cell mediated mechanisms in ongoing allograft injury.

Original languageEnglish (US)
Article number6218
JournalInternational Journal of Molecular Sciences
Volume22
Issue number12
DOIs
StatePublished - Jun 2 2021

Keywords

  • Circulating small non-coding RNAs
  • MiRNAs
  • Non-invasive biomarker
  • RNA-seq
  • TRNA frag-ments
  • Transplant glomerulopathy

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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