{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:48:07Z","timestamp":1788299287581,"version":"build-2803163510"},"reference-count":27,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T00:00:00Z","timestamp":1684195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for Scientific Research (C)","award":["M.K. 22K08077"],"award-info":[{"award-number":["M.K. 22K08077"]}]},{"name":"Grant-in-Aid for Scientific Research (C)","award":["T.A. 17H04200"],"award-info":[{"award-number":["T.A. 17H04200"]}]},{"name":"Grant-in-Aid for Scientific Research (C)","award":["20H03732"],"award-info":[{"award-number":["20H03732"]}]},{"name":"Grant-in-Aid for Scientific Research (B)","award":["M.K. 22K08077"],"award-info":[{"award-number":["M.K. 22K08077"]}]},{"name":"Grant-in-Aid for Scientific Research (B)","award":["T.A. 17H04200"],"award-info":[{"award-number":["T.A. 17H04200"]}]},{"name":"Grant-in-Aid for Scientific Research (B)","award":["20H03732"],"award-info":[{"award-number":["20H03732"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Our previous studies using rodent models have suggested an essential role for Pin1 in the pathogenesis of non-alcoholic steatohepatitis (NASH). In addition, interestingly, serum Pin1 elevation has been reported in NASH patients. However, no studies have as yet examined the Pin1 expression level in human NASH livers. To clarify this issue, we investigated the expression level and subcellular distribution of Pin1 in liver specimens obtained using needle-biopsy samples from patients with NASH and healthy liver donors. Immunostaining using anti-Pin1 antibody revealed the Pin1 expression level to be significantly higher, particularly in nuclei, in the livers of NASH patients than those of healthy donors. In the samples from patients with NASH, the amount of nuclear Pin1 was revealed to be negatively related to serum alanine aminotransferase (ALT), while tendencies to be associated with other serum parameters such as aspartate aminotransferase (AST) and platelet number were noted but did not reach statistical significance. Such unclear results and the lack of a significant relationship might well be attributable to our small number of NASH liver samples (n = 8). Moreover, in vitro, it was shown that addition of free fatty acids to medium induced lipid accumulation in human hepatoma HepG2 and Huh7 cells, accompanied with marked increases in nuclear Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1), in accordance with the aforementioned observations in human NASH livers. In contrast, suppression of Pin1 gene expression using siRNAs attenuated the free fatty acid-induced lipid accumulation in Huh7 cells. Taken together, these observations strongly suggest that increased expression of Pin1, particularly in hepatic nuclei, contributes to the pathogenesis of NASH with lipid accumulation.<\/jats:p>","DOI":"10.3390\/ijms24108847","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T02:04:05Z","timestamp":1684289045000},"page":"8847","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hepatic Pin1 Expression, Particularly in Nuclei, Is Increased in NASH Patients in Accordance with Evidence of the Role of Pin1 in Lipid Accumulation Shown in Hepatoma Cell Lines"],"prefix":"10.3390","volume":"24","author":[{"given":"Machi","family":"Kanna","sequence":"first","affiliation":[{"name":"Department of Medical Science, Graduate School of Medicine, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Nakatsu","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Graduate School of Medicine, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Yamamotoya","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Graduate School of Medicine, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1385-7487","authenticated-orcid":false,"given":"Akifumi","family":"Kushiyama","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy, Meiji Pharmaceutical University, 2-522-1, Kiyose 204-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midori","family":"Fujishiro","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Sakoda","sequence":"additional","affiliation":[{"name":"Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiraku","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Arihiro","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoichiro","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Graduate School of Medicine, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Berardo, C., Di Pasqua, L.G., Cagna, M., Richelmi, P., Vairetti, M., and Ferrigno, A. 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