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[The biological activity of MHC classII transactivator ribonuclease P: a novel approach for hepatic transplantation rejection]. | LitMetric

AI Article Synopsis

  • - The study aimed to analyze how RNaseP affects the CIITA gene in regulating class II MHC (MHCII) expression.
  • - Researchers created a specific RNA guide (M1-629-GS) that targets and cleaves the CIITA mRNA, leading to reduced expression of MHCII molecules on hepatocytes when stimulated with IFN-gamma.
  • - Results showed that this RNA guide effectively lowered CIITA mRNA levels and MHCII expression significantly, suggesting its potential use as a novel treatment to prevent organ rejection in liver transplants.

Article Abstract

Objective: This paper studied the effect of RNaseP against CIITA on repressing class II MHC (MHCII) expression.

Methods: It was constructed that M1-RNA with guide sequences (GS), recognizing the 629 site of CIITA (M1-629-GS), by PCR from pTK117 plasmid, then was cloned into psNAV (psNAV-M1-629-GS). CIITA target gene was obtained from Raji cell by RT-PCR, and then inserted into pGEM-7zf (+) (pGEM-800). psNAV-M1-629-GS and pGEM-800 were transcribed and then mixed up and incubated in vitro. Stable transfectants of hepatocyte with psNAV-M1-629-GS by nanometer were tested for MHCII induction by recombinant human interferon-gamma (IFN-gamma). mRNA abundance of CIITA was measured by RT-PCR.

Results: It showed that M1-629-GS could exclusively cleave pGEM-800 that formed a base pair with the GS. When induced with IFN-gamma, the expression of HLA-DR, -DP, -DQ on psNAV-M1-629-GS+ hepatocyte was (1.01+/-0.51)%, (4.37+/-1.28)%, (1.98+/-0.42)% respectively, was down-modulated 90.65%, 89.11% and 65.32% compared with control, while the mRNA content of CIITA reduced significantly (P<0.01).

Conclusion: M1-629-GS could effectively repress MHCII expressing through cleaving CIITA mRNA. These results provided insight into the future application of it as a new nucleic acid drug against the rejection of hepatic transplantation.

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