Open AccessReduction in SNAP-23 Alters Microfilament Organization in Myofibrobastic Hepatic Stellate Cells
Author(s) -
Haleigh B Eubanks,
Élise G. Lavoie,
Jessica R. Goree,
Jeffrey A. Kamykowski,
Neriman Gökden,
Michel Fausther,
Jonathan A. Dranoff
Publication year - 2020
Publication title -
gene expression
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 46
eISSN - 1555-3884
pISSN - 1052-2166
DOI - 10.3727/105221619x15742818049365
Subject(s) - hepatic stellate cell , microbiology and biotechnology , snap , actin , downregulation and upregulation , cytoskeleton , fibrosis , microfilament , in vivo , phenotype , biology , chemistry , cell , pathology , medicine , endocrinology , biochemistry , genetics , gene , computer science , computer graphics (images)
Hepatic stellate cells (HSC) are critical effector cells of liver fibrosis. In the injured liver, HSC differentiate into a myofibrobastic phenotype. A critical feature distinguishing myofibroblastic from quiescent HSC is cytoskeletal reorganization. Soluble NSF attachment receptor (SNARE) proteins are important in trafficking of newly synthesized proteins to the plasma membrane for release into the extracellular environment. The goals of this project were to determine the expression of specific SNARE proteins in myofibroblastic HSC and to test whether their alteration changed the HSC phenotype in vitro and progression of liver fibrosis in vivo. We found that HSC lack the t-SNARE protein, SNAP-25, but express a homologous protein, SNAP-23. Downregulation of SNAP-23 in HSC induced reduction in polymerization and disorganization of the actin cytoskeleton associated with loss of cell movement. In contrast, reduction in SNAP-23 in mice by monogenic deletion delayed but did not prevent progression of liver fibrosis to cirrhosis. Taken together, these findings suggest that SNAP-23 is an important regular of actin dynamics in myofibroblastic HSC, but that the role of SNAP-23 in the progression of liver fibrosis in vivo is unclear.