Identification of Potential Leukocyte Biomarkers Related to Drug Recovery of CFTR: Clinical Applications in Cystic Fibrosis

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Apr 30

PMID 33920274

Citations 8

Authors

Marco Pedrazzi

Silvia Vercellone

Elettra Barberis

Michela Capraro

Roberta De Tullio

Federico Cresta

Rosaria Casciaro

Carlo Castellani

Mauro Patrone

Emilio Marengo

Paola Lecca

Paola Melotti

Claudio Sorio

Marcello Manfredi

Monica Averna

Affiliations

Soon will be listed here.

Abstract

The aim of this study was the identification of specific proteomic profiles, related to a restored cystic fibrosis transmembrane conductance regulator (CFTR) activity in cystic fibrosis (CF) leukocytes before and after ex vivo treatment with the potentiator VX770. We used leukocytes, isolated from CF patients carrying residual function mutations and eligible for Ivacaftor therapy, and performed CFTR activity together with proteomic analyses through micro-LC-MS. Bioinformatic analyses of the results obtained revealed the downregulation of proteins belonging to the leukocyte transendothelial migration and regulation of actin cytoskeleton pathways when CFTR activity was rescued by VX770 treatment. In particular, we focused our attention on matrix metalloproteinase 9 (MMP9), because the high expression of this protease potentially contributes to parenchyma lung destruction and dysfunction in CF. Thus, the downregulation of MMP9 could represent one of the possible positive effects of VX770 in decreasing the disease progression, and a potential biomarker for the prediction of the efficacy of therapies targeting the defect of Cl transport in CF.

Citing Articles

Lung Inflammatory Genes in Cystic Fibrosis and Their Relevance to Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapies.

Carbone A, Vitullo P, Di Gioia S, Conese M Genes (Basel). 2023; 14(10).

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Modulation of Plasmatic Matrix Metalloprotease 9: A Promising New Tool for Understanding the Variable Clinical Responses of Patients with Cystic Fibrosis to Cystic Fibrosis Transmembrane Conductance Regulator Modulators.

Capraro M, Pedrazzi M, De Tullio R, Manfredi M, Cresta F, Castellani C Int J Mol Sci. 2023; 24(17).

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Discovery of dysregulated circular RNAs in whole blood transcriptomes from cystic fibrosis patients - implication of a role for cellular senescence in cystic fibrosis.

Salinas E, Macauley V, Keeling K, Edwards Y J Cyst Fibros. 2023; 22(4):683-693.

PMID: 37142522 PMC: 10947771. DOI: 10.1016/j.jcf.2023.04.021.

Impact of Modulators on the Impaired Function of Phagocytes in Cystic Fibrosis Lung Disease.

Meoli A, Eickmeier O, Pisi G, Fainardi V, Zielen S, Esposito S Int J Mol Sci. 2022; 23(20).

PMID: 36293274 PMC: 9604330. DOI: 10.3390/ijms232012421.

Emerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis.

Jaganathan D, Bruscia E, Kopp B Int J Mol Sci. 2022; 23(14).

PMID: 35887098 PMC: 9319215. DOI: 10.3390/ijms23147750.

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