MIR-126和MMP9在腹腔内瘘管形成型克罗恩病发病机制中的作用：简要研究报告

Involvement of MIR-126 and MMP9 in the Pathogenesis of Intra-Abdominal Fistulizing Crohn's Disease: A Brief Research Report.

作者信息

Luceri Cristina, D'Ambrosio Mario, Bigagli Elisabetta, Cinci Lorenzo, Russo Edda, Staderini Fabio, Cricchio Marta, Giudici Francesco, Scaringi Stefano

机构信息

Department of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy.

Department of Surgery and Translational Medicine, Section of Surgery, University of Florence, Florence, Italy.

出版信息

Front Surg. 2022 May 10;9:822407. doi: 10.3389/fsurg.2022.822407. eCollection 2022.

DOI:10.3389/fsurg.2022.822407

PMID:35620197

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9127299/

Abstract

BACKGROUND

Intra-abdominal fistulas are complications that affect a significant proportion of Crohn's disease patients, often requiring surgery. The aim of the present work was to correlate the occurrence of intestinal fistulization to the clinico-pathological features of these patients and to the plasma levels of MMP9, a gelatinase involved in the pathophysiology of fistula formation, and of miR-126, appearing to modulate MMP9 expression.

METHODS

In a series of 31 consecutive Crohn's patients admitted to surgery due to therapeutic failure and/or complicated disease, we identified nine cases of abdominal fistulas, mainly entero-enteric fistulas. MMP9 protein was determined in plasma and at the intestinal level using immunometric assays. Circulating miR-126 was also measured in all plasma samples by real-time PCR.

RESULTS

Comparing patients with and without intra-abdominal fistulas, we did not observe differences in terms of age, gender, disease location and duration, number of previous surgeries and pre-biologic medications. However, cases with intra-abdominal fistulas had a significantly higher CDAI ( < 0.0001) and a significantly lower circulating miR-126 ( < 0.05). Patients with intra-abdominal fistulas had also a significantly higher amount of circulating MMP9 ( < 0.0001) and this data was correlated with an increased expression of MMP9 protein in the mucosa and with reduced levels of circulating miR-126. Receiver operating characteristic (ROC) analysis pointed out the ability of circulating MMP9 to discriminate patients with and without intra-abdominal fistulas.

CONCLUSIONS

These data confirm that circulating MMP9 can be used for the identification of cases with intra-abdominal fistulas and suggest that miR-126 may be also involved in the pathogenesis of this complication and that it may be further investigated as a new therapeutic strategy or for monitoring therapeutic response in these patients.

摘要

背景

腹腔内瘘是影响相当一部分克罗恩病患者的并发症，常需手术治疗。本研究的目的是将肠瘘的发生与这些患者的临床病理特征、参与瘘管形成病理生理过程的明胶酶MMP9的血浆水平以及似乎可调节MMP9表达的miR - 126相关联。

方法

在一系列因治疗失败和/或疾病复杂而接受手术的31例连续克罗恩病患者中，我们确定了9例腹腔瘘病例，主要为肠 - 肠瘘。使用免疫测定法在血浆和肠道水平测定MMP9蛋白。还通过实时PCR在所有血浆样本中测量循环miR - 126。

结果

比较有和没有腹腔内瘘的患者，我们未观察到年龄、性别、疾病部位和病程、既往手术次数和生物制剂前用药方面的差异。然而，有腹腔内瘘的病例CDAI显著更高（<0.0001），循环miR - 126显著更低（<0.05）。有腹腔内瘘的患者循环MMP9量也显著更高（<0.0001），并且该数据与黏膜中MMP9蛋白表达增加以及循环miR - 126水平降低相关。受试者工作特征（ROC）分析指出循环MMP9区分有和没有腹腔内瘘患者的能力。