Integrative Analyses of Circulating Small RNAs and Kidney Graft Transcriptome in Transplant Glomerulopathy.
RNA-seq
circulating small non-coding RNAs
miRNAs
non-invasive biomarker
tRNA fragments
transplant glomerulopathy
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
09 Jun 2021
09 Jun 2021
Historique:
received:
13
04
2021
revised:
01
06
2021
accepted:
06
06
2021
entrez:
2
7
2021
pubmed:
3
7
2021
medline:
22
7
2021
Statut:
epublish
Résumé
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 glomerulopathy. 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 allograft 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.
Identifiants
pubmed: 34207555
pii: ijms22126218
doi: 10.3390/ijms22126218
pmc: PMC8226568
pii:
doi:
Substances chimiques
Cell-Free Nucleic Acids
0
MicroRNAs
0
RNA, Transfer, Gly
0
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK117183
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK080074
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01DK109581, R01DK122682
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK122682
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK109581
Pays : United States
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