OBJECTIVE: Liver fibrosis results from the perpetuation of the normal wound healing response to several types of injury. Despite the wealth of knowledge regarding the involvement of intracellular and extracellular signaling pathways in liver fibrogenesis, information about the role of intercellular communication mediated by gap junctions is scarce. METHODS: In this study, liver fibrosis was chemically induced by carbon tetrachloride in mice lacking connexin32, the major liver gap junction constituent. The manifestation of liver fibrosis was evaluated based on a series of read-outs, including collagen morphometric and mRNA analysis, oxidative stress, apoptotic, proliferative and inflammatory markers. RESULTS: More pronounced liver damage and enhanced collagen deposition were observed in connexin32 knockout mice compared to wild-type animals in experimentally triggered induced liver fibrosis. No differences between both groups were noticed in apoptotic signaling nor in inflammation markers. However, connexin32 deficient mice displayed decreased catalase activity and increased malondialdehyde levels. CONCLUSION: These findings could suggest that connexin32-based signaling mediates tissue resistance against liver damage by the modulation of the antioxidant capacity. In turn, this could point to a role for connexin32 signaling as a therapeutic target in the treatment of liver fibrosis.
OBJECTIVE: Liver fibrosis results from the perpetuation of the normal wound healing response to several types of injury. Despite the wealth of knowledge regarding the involvement of intracellular and extracellular signaling pathways in liver fibrogenesis, information about the role of intercellular communication mediated by gap junctions is scarce. METHODS: In this study, liver fibrosis was chemically induced by carbon tetrachloride in mice lacking connexin32, the major liver gap junction constituent. The manifestation of liver fibrosis was evaluated based on a series of read-outs, including collagen morphometric and mRNA analysis, oxidative stress, apoptotic, proliferative and inflammatory markers. RESULTS: More pronounced liver damage and enhanced collagen deposition were observed in connexin32 knockout mice compared to wild-type animals in experimentally triggered induced liver fibrosis. No differences between both groups were noticed in apoptotic signaling nor in inflammation markers. However, connexin32 deficient mice displayed decreased catalase activity and increased malondialdehyde levels. CONCLUSION: These findings could suggest that connexin32-based signaling mediates tissue resistance against liver damage by the modulation of the antioxidant capacity. In turn, this could point to a role for connexin32 signaling as a therapeutic target in the treatment of liver fibrosis.
Authors: Bruno Cogliati; Hélder de Moraes Pereira; Maria Lúcia Zaidan Dagli; Osório Miguel Parra; José Roberto Machado Cunha da Silva; Francisco Javier Hernandez-Blazquez Journal: Arq Gastroenterol Date: 2010 Jan-Mar
Authors: Hernán E González; Eliseo A Eugenín; Gladys Garcés; Nancy Solís; Margarita Pizarro; Luigi Accatino; Juan C Sáez Journal: Am J Physiol Gastrointest Liver Physiol Date: 2002-06 Impact factor: 4.052
Authors: Jean-Louis Frossard; Laura Rubbia-Brandt; Matthew A Wallig; Messod Benathan; Thomas Ott; Philippe Morel; Antoine Hadengue; Susanne Suter; Klaus Willecke; Marc Chanson Journal: Gastroenterology Date: 2003-02 Impact factor: 22.682
Authors: Halyna M Kuznietsova; Natalia V Dziubenko; Oksana V Lynchak; Tetyana S Herheliuk; Dmytro K Zavalny; Olga V Remeniak; Yuriy I Prylutskyy; Uwe Ritter Journal: Dig Dis Sci Date: 2019-07-16 Impact factor: 3.199
Authors: Sara Crespo Yanguas; Tereza C da Silva; Isabel V A Pereira; Michaël Maes; Joost Willebrords; Valery I Shestopalov; Bruna M Goes; Marina Sayuri Nogueira; Inar Alves de Castro; Guilherme R Romualdo; Luís F Barbisan; Eva Gijbels; Mathieu Vinken; Bruno Cogliati Journal: Arch Toxicol Date: 2018-07-09 Impact factor: 5.153
Authors: Sara Crespo Yanguas; Tereza C da Silva; Isabel V A Pereira; Joost Willebrords; Michaël Maes; Marina Sayuri Nogueira; Inar Alves de Castro; Isabelle Leclercq; Guilherme R Romualdo; Luís F Barbisan; Luc Leybaert; Bruno Cogliati; Mathieu Vinken Journal: Int J Mol Sci Date: 2018-03-12 Impact factor: 5.923