Faculty, Staff and Student Publications

Language

English

Publication Date

10-1-2023

Journal

Clinical and Translational Medicine

DOI

10.1002/ctm2.1434

PMID

37846205

PMCID

PMC10579997

PubMedCentral® Posted Date

10-17-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Specific microRNAs (miRNAs) were elevated in chronic pancreatitis (CP) patients during islet infusion after total pancreatectomy (TPIAT). We aimed to identify circulating miRNA signatures of pancreatic damage, predict miRNA-mRNA networks to identify potential links to CP pathogenesis and identify islet isolation and transplantation functional outcomes.

Methods: Small RNA sequencing was performed to identify distinct circulating miRNA signatures in CP. Plasma miRNAs were measured using miRCURY LNA SYBR green quantitative real-time polymerase chain reaction assays. Correlation analyses were performed using R software. The miRNA target and disease interactions were determined using miRNet and the miRNA enrichment and annotation tool.

Results: Alterations were found in circulating miRNAs in CP patients compared to healthy controls. Further studies were conducted on 12 circulating miRNAs enriched in the pancreas, other tissues and other diseases including cancer and fibrosis. Approximately 2888 mRNAs in the pancreas were their targets, demonstrating interactions with 76 small molecules. Three miRNAs exhibited interactions with morphine and five exhibited interactions with glucose. The miRNA panel targeted 22 genes associated with pancreatitis. The islet-specific, acinar cell-specific and liver-specific miRNAs were elevated at 6 h after islet infusion and returned to baseline levels 3 months after TPIAT. Circulating levels of miRNAs returned to pre-transplant levels 1-year post-transplant. Circulating miRNAs measured before and 6 h after islet infusion were directly or inversely associated with metabolic outcomes at 3 and 6 months post-transplant.

Conclusions: miRNAs may contribute to CP pathogenesis, and elevated circulating levels may be specific to pancreatic inflammation and fibrosis, warranting further investigation.

Keywords

Humans, Pancreatectomy, Transplantation, Autologous, Circulating MicroRNA, Islets of Langerhans Transplantation, Pancreatitis, Chronic, MicroRNAs, Fibrosis, biomarkers, chronic pancreatitis, circulating miRNAs, islet autotransplantation

Published Open-Access

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