| 2. |
- Panzitt, Katrin, et al.
(author)
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FXR-dependent Rubicon induction impairs autophagy in models of human cholestasis.
- 2020
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In: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 72:6, s. 1122-1131
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Journal article (peer-reviewed)abstract
- Cholestasis comprises a spectrum of liver diseases characterized by the accumulation of bile acids. Bile acids and activation of the farnesoid X receptor (FXR) can inhibit autophagy, a cellular self-digestion process necessary for cellular homeostasis and regeneration. In mice, autophagy appears to be impaired in cholestasis and induction of autophagy may reduce liver injury.Herein, we explored autophagy in human cholestasis invivo and investigated the underlying molecular mechanisms invitro. FXR chromatin immunoprecipitation-sequencing and qPCR were performed in combination with luciferase promoter studies to identify functional FXR binding targets in a human cholestatic liver sample.Autophagic processing appeared to be impaired in patients with cholestasis and in individuals treated with the FXR ligand obeticholic acid (OCA). Invitro, chenodeoxycholic acid and OCA inhibited autophagy at the level of autophagosome to lysosome fusion in an FXR-dependent manner. Rubicon, which inhibits autophago-lysosomal maturation, was identified as a direct FXR target that is induced in cholestasis and by FXR-agonistic bile acids. Genetic inhibition of Rubicon reversed the bile acid-induced impairment of autophagic flux. In contrast to OCA, ursodeoxycholic acid (UDCA), which is a non-FXR-agonistic bile acid, induced autophagolysosome formation independently of FXR, enhanced autophagic flux and was associated with reduced Rubicon levels.In models of human cholestasis, autophagic processing is impaired in an FXR-dependent manner, partly resulting from the induction of Rubicon. UDCA is a potent inducer of hepatic autophagy. Manipulating autophagy and Rubicon may represent a novel treatment concept for cholestatic liver diseases.Autophagy, a cellular self-cleansing process, is impaired in various forms of human cholestasis. Bile acids, which accumulate in cholestatic liver disease, induce Rubicon, a protein that inhibits proper execution of autophagy. Ursodeoxycholic acid, which is the first-line treatment option for many cholestatic liver diseases, induces hepatic autophagy along with reducing Rubicon.
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| 3. |
- Rimmel, Gunnar, 1971, et al.
(author)
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Intellectual capital disclosures in Japanese IPO prospectuses
- 2009
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In: Journal of Human Resource Costing & Accounting. - 1401-338X. ; 13:4, s. 316-337
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Journal article (peer-reviewed)abstract
- Purpose – The purpose of this paper is to give an indication of the quantity of intellectual capital information in Japanese initial public offering (IPO) prospectuses from all stock exchange listings on the Japan Stock Exchange from 2003. Design/methodology/approach – The paper applied a disclosure index consisting of 78 items to quantify the amount of information regarding intellectual capital included in the IPO prospectuses of Japanese companies. An analysis of variance (ANOVA) was used to test, controlling for technological type of the company (high-tech/low-tech), and whether the extent of managerial ownership prior to the IPO, company age and company size influenced disclosure. Findings – From the analyses conclusions are derived for four hypotheses. The hypotheses “industry differences” (H1), “managerial ownership” (H2) and “company size” (H3) were found not to be significant factors explaining voluntary disclosure of information. The fourth factor, “company age” (H4), did, however, have a significant influence on the extent of disclosure for Japanese companies. Further testing of the Japanese companies regarding age showed a continuing trend. Originality/value – Although Japan has been strongly associated with the concept of the knowledge society, Japanese studies regarding intellectual capital have been very scarce. No studies, to the best of one's knowledge, have examined the specific disclosure of intellectual capital information included in Japanese IPO prospectuses.
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