Dataset Information

Cholestasis induces reversible accumulation of periplakin in mouse liver.

ABSTRACT: Periplakin (PPL) is a rod-shaped cytolinker protein thought to connect cellular adhesion junctional complexes to cytoskeletal filaments. PPL serves as a structural component of the cornified envelope in the skin and interacts with various types of proteins in cultured cells; its level decreases dramatically during tumorigenic progression in human epithelial tissues. Despite these intriguing observations, the physiological roles of PPL, especially in non-cutaneous tissues, are still largely unknown. Because we observed a marked fluctuation of PPL expression in mouse liver in association with the bile acid receptor farnesoid X receptor (FXR) and cholestasis, we sought to characterize the role of PPL in the liver and determine its contributions to the etiology and pathogenesis of cholestasis.Time- and context-dependent expression of PPL in various mouse models of hepatic and renal disorders were examined by immunohistochemistry, western blotting, and quantitative real-time polymerase chain reactions.The hepatic expression of PPL was significantly decreased in Fxr-/- mice. In contrast, the expression was dramatically increased during cholestasis, with massive PPL accumulation observed at the boundaries of hepatocytes in wild-type mice. Interestingly, the hepatic accumulation of PPL resulting from cholestasis was reversible. In addition, similar accumulation of PPL at cellular boundaries was found in epithelial cells around renal tubules upon ureteral obstruction.PPL may be involved in the temporal accommodation to fluid stasis in different tissues. Further examination of the roles for PPL may lead to the discovery of a novel mechanism for cellular protection by cytolinkers that is applicable to many tissues and in many contexts.

SUBMITTER: Ito S

PROVIDER: S-EPMC3716950 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cholestasis induces reversible accumulation of periplakin in mouse liver.

Ito Shinji S Satoh Junko J Matsubara Tsutomu T Shah Yatrik M YM Ahn Sung-hoon SH Anderson Cherie R CR Shan Weiwei W Peters Jeffrey M JM Gonzalez Frank J FJ

BMC gastroenterology 20130713

<h4>Background</h4>Periplakin (PPL) is a rod-shaped cytolinker protein thought to connect cellular adhesion junctional complexes to cytoskeletal filaments. PPL serves as a structural component of the cornified envelope in the skin and interacts with various types of proteins in cultured cells; its level decreases dramatically during tumorigenic progression in human epithelial tissues. Despite these intriguing observations, the physiological roles of PPL, especially in non-cutaneous tissues, are ...[more]

PMID: 23849208

Similar Datasets

Project description:Sirtuin1 (Sirt1; mammalian homolog of Saccharomyces cerevisiae enzyme Sir2) is a transcriptional and transactivational regulator of murine farnesoid X receptor (Fxr), which is the primary bile acid (BA) sensor, and critical regulator of BA metabolism in physiological and pathophysiological conditions. Previous studies have suggested compromised Sirt1 expression in rodent models of cholestatic liver injury. We hypothesized that Sirt1 could be potentially targeted to alleviate cholestatic liver injury. In cultured primary human hepatocytes, SIRT1 messenger RNA was down-regulated after GCA treatment, potentially through induction of microRNA (miR)-34a, whereas tauroursodeoxycholic acid induced SIRT1 expression without affecting miR-34a expression. Sirt1 expression was also significantly down-regulated in three mouse models of liver injury (bile duct ligation, 1% cholic acid [CA] fed, and the Mdr2-/- mouse). Mice fed CA diet also demonstrated hepatic FXR hyperacetylation and induction of the Janus kinase/p53 pathway. Mice fed a CA diet and concurrently administered the Sirt1 activator, SRT1720 (50 mg/kg/day, orally), demonstrated 40% and 45% decrease in plasma alanine aminotransferase and BA levels, respectively. SRT1720 increased hepatic BA hydrophilicity by increasing tri- and tetrahydroxylated and decreasing the dihydroxylated BA fraction. SRT1720 administration also inhibited hepatic BA synthesis, potentially through ileal fibroblast growth factor 15- and Fxr-mediated inhibition of cytochrome p450 (Cyp) 7a1 and Cyp27a1, along with increased hepatic BA hydroxylation in association with Cyp2b10 induction. SRT1720 administration significantly induced renal multidrug resistance-associated protein 2 and 4, peroxisome proliferator-activated receptor gamma coactivator 1-?, and constitutive androstance receptor expression along with ?2-fold increase in urinary BA concentrations.SRT1720 administration alleviates cholestatic liver injury in mice by increasing hydrophilicity of hepatic BA composition and decreasing plasma BA concentration through increased BA excretion into urine. Thus, use of small-molecule activators of Sirt1 presents a novel therapeutic target for cholestatic liver injury. (Hepatology 2016;64:2151-2164).

Dataset Information

Cholestasis induces reversible accumulation of periplakin in mouse liver.

Publications

Cholestasis induces reversible accumulation of periplakin in mouse liver.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets