title: Cholestasis induces reversible accumulation of periplakin in mouse liver.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Biofrontier Platform, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. ito.shinji.3v@kyoto-u.ac.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Ito
authors.forename: Junko
authors.initials: J
authors.lastname: Satoh
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Matsubara
authors.forename: Yatrik M
authors.initials: YM
authors.lastname: Shah
authors.forename: Sung-hoon
authors.initials: SH
authors.lastname: Ahn
authors.forename: Cherie R
authors.initials: CR
authors.lastname: Anderson
authors.forename: Weiwei
authors.initials: W
authors.lastname: Shan
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Peters
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
mesh_terms: D000818:Animals; D002779:Cholestasis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D003208:Concanavalin A; D004847:Epithelial Cells; D015870:Gene Expression; D022781:Hepatocytes; D007684:Kidney Tubules / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051179:Plakins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D014517:Ureteral Obstruction / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D003208:Concanavalin A; D051179:Plakins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C110037:Ppl protein, mouse