Paradoxical Role of Matrix Metalloproteinases in Liver Injury and Regeneration after Sterile Acute Hepatic Failure.

Autor: Alvarenga DM; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. deboraalvarengabio@gmail.com., Mattos MS; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. mattosms@yahoo.com.br., Lopes ME; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. mateuslopes_12@hotmail.com., Marchesi SC; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. sarahcmarchesi@gmail.com., Araújo AM; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. amoreiradearaujo@gmail.com., Nakagaki BN; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. brendanaemi22@gmail.com., Santos MM; Departamento de Biologia Animal, Universidade Federal De Viçosa, Viçosa 36570-900, Brazil. monicamoraissantos@gmail.com., David BA; Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 4N1, Canada. brunaraujodavid@gmail.com., De Souza VA; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. viviane_lacerda@outlook.com., Carvalho É; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. erikacarvalhobio@gmail.com., Sousa Pereira RV; The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada. rafaelavazsp@gmail.com., Marques PE; The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada. pempsufmg@gmail.com., Mafra K; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. kassiana93@gmail.com., de Castro Oliveira HM; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. hortsmaciel@gmail.com., de Miranda CDM; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. camiladutra_mm@hotmail.com., Diniz AB; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. abarrosdiniz@gmail.com., de Oliveira THC; Departamento de Bioquímica e Imunologia, Laboratório de Imunofarmacologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. thiagohcoliveira@gmail.com., Teixeira MM; Departamento de Bioquímica e Imunologia, Laboratório de Imunofarmacologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. mmtex.ufmg@gmail.com., Rezende RM; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. rafaelmachadorezende@gmail.com., Antunes MM; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. maisaantunes@gmail.com., Menezes GB; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. menezesgb@ufmg.br.
Jazyk: angličtina
Zdroj: Cells [Cells] 2018 Dec 06; Vol. 7 (12). Date of Electronic Publication: 2018 Dec 06.
DOI: 10.3390/cells7120247
Abstrakt: Acetaminophen (APAP) poisoning is one of the leading causes of acute hepatic failure and liver transplantation is often the only lifesaving alternative. During the course of hepatocyte necrosis, an intense accumulation of neutrophils is often observed within the liver microenvironment. Despite the classic idea that neutrophil accumulation in tissues causes collateral tissue damage, there is a growing body of evidence showing that neutrophils can also orchestrate the resolution of inflammation. In this work, drug-induced liver injury was induced by oral administration of APAP and pharmacological intervention was made 12 h after this challenge. Liver injury and repair kinetics were evaluated by a novel combination of enzyme quantifications, ELISA, specific antagonists of neutrophil enzymes and confocal intravital microscopy. We have demonstrated that neutrophil infiltration is not only involved in injury amplification, but also in liver tissue repair after APAP-induced liver injury. In fact, while neutrophil depletion led to reduced hepatic necrosis during APAP poisoning, injury recovery was also delayed in neutropenic mice. The mechanisms underlying the neutrophil reparative role involved rapid degranulation and matrix metalloproteinases (MMPs) activity. Our data highlights the crucial role of neutrophils, in particular for MMPs, in the resolution phase of APAP-induced inflammatory response.
Databáze: MEDLINE
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