{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:50:48Z","timestamp":1780339848323,"version":"3.54.1"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wilhelm Sander Stiftung","award":["2020.002.1"],"award-info":[{"award-number":["2020.002.1"]}]},{"name":"Wilhelm Sander Stiftung","award":["102\/20"],"award-info":[{"award-number":["102\/20"]}]},{"name":"Wilhelm Sander Stiftung","award":["WE2554\/13-1"],"award-info":[{"award-number":["WE2554\/13-1"]}]},{"name":"Wilhelm Sander Stiftung","award":["WE2554\/15-1"],"award-info":[{"award-number":["WE2554\/15-1"]}]},{"name":"Wilhelm Sander Stiftung","award":["WE2554\/17-1"],"award-info":[{"award-number":["WE2554\/17-1"]}]},{"name":"START program","award":["2020.002.1"],"award-info":[{"award-number":["2020.002.1"]}]},{"name":"START program","award":["102\/20"],"award-info":[{"award-number":["102\/20"]}]},{"name":"START program","award":["WE2554\/13-1"],"award-info":[{"award-number":["WE2554\/13-1"]}]},{"name":"START program","award":["WE2554\/15-1"],"award-info":[{"award-number":["WE2554\/15-1"]}]},{"name":"START program","award":["WE2554\/17-1"],"award-info":[{"award-number":["WE2554\/17-1"]}]},{"name":"German Research Foundation","award":["2020.002.1"],"award-info":[{"award-number":["2020.002.1"]}]},{"name":"German Research Foundation","award":["102\/20"],"award-info":[{"award-number":["102\/20"]}]},{"name":"German Research Foundation","award":["WE2554\/13-1"],"award-info":[{"award-number":["WE2554\/13-1"]}]},{"name":"German Research Foundation","award":["WE2554\/15-1"],"award-info":[{"award-number":["WE2554\/15-1"]}]},{"name":"German Research Foundation","award":["WE2554\/17-1"],"award-info":[{"award-number":["WE2554\/17-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perilipin 5 (PLIN5) is a lipid droplet coat protein that is highly expressed in oxidative tissues such as those of muscles, the heart and the liver. PLIN5 expression is regulated by a family of peroxisome proliferator-activated receptors (PPARs) and modulated by the cellular lipid status. So far, research has focused on the role of PLIN5 in the context of non-alcoholic fatty liver disease (NAFLD) and specifically in lipid droplet formation and lipolysis, where PLIN5 serves as a regulator of lipid metabolism. In addition, there are only limited studies connecting PLIN5 to hepatocellular carcinoma (HCC), where PLIN5 expression is proven to be upregulated in hepatic tissue. Considering that HCC development is highly driven by cytokines present throughout NAFLD development and in the tumor microenvironment, we here explore the possible regulation of PLIN5 by cytokines known to be involved in HCC and NAFLD progression. We demonstrate that PLIN5 expression is strongly induced by interleukin-6 (IL-6) in a dose- and time-dependent manner in Hep3B cells. Moreover, IL-6-dependent PLIN5 upregulation is mediated by the JAK\/STAT3 signaling pathway, which can be blocked by transforming growth factor-\u03b2 (TGF-\u03b2) and tumor necrosis factor-\u03b1 (TNF-\u03b1). Furthermore, IL-6-mediated PLIN5 upregulation changes when IL-6 trans-signaling is stimulated through the addition of soluble IL-6R. In sum, this study sheds light on lipid-independent regulation of PLIN5 expression in the liver, making PLIN5 a crucial target for NAFLD-induced HCC.<\/jats:p>","DOI":"10.3390\/ijms24087219","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T02:28:12Z","timestamp":1681439292000},"page":"7219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Lipid-Independent Regulation of PLIN5 via IL-6 through the JAK\/STAT3 Axis in Hep3B Cells"],"prefix":"10.3390","volume":"24","author":[{"given":"Marinela","family":"Krizanac","sequence":"first","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola Berenice","family":"Mass Sanchez","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-3726","authenticated-orcid":false,"given":"Sarah K.","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-0931","authenticated-orcid":false,"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5924-5956","authenticated-orcid":false,"given":"Anastasia","family":"Asimakopoulos","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S361","DOI":"10.21037\/jgo.2020.02.08","article-title":"Addressing the worldwide hepatocellular carcinoma: Epidemiology, prevention and management","volume":"12","author":"Samant","year":"2021","journal-title":"J. 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