{"id":1396,"date":"2025-02-14T14:09:14","date_gmt":"2025-02-14T14:09:14","guid":{"rendered":"https:\/\/amm-journal.org\/?p=1396"},"modified":"2025-02-14T14:09:14","modified_gmt":"2025-02-14T14:09:14","slug":"estrogen-induced-cholestasis","status":"publish","type":"post","link":"https:\/\/amm-journal.org\/index.php\/2025\/02\/14\/estrogen-induced-cholestasis\/","title":{"rendered":"MiR-128-3p mediates MRP2 internalization in estrogen-induced cholestasis through targeting PDZK1"},"content":{"rendered":"

Announcing a new publication for Acta Materia Medica<\/em> journal<\/a>. Estrogens have been reported to cause dysfunction in biliary transport systems, thereby inducing cholestasis. Multidrug resistance-associated protein 2 (MRP2) is a transporter responsible for independent bile flow. Emerging evidence indicates that PDZ domain containing 1 (PDZK1) regulates localization of MRP2; however, PDZK1\u2019s role and regulatory machinery in MRP2-mediated estrogen-induced cholestasis (EIC) remain unclear.<\/p>\n

The authors of this article observed, in a mouse model of EIC, downregulated PDZK1 expression in the liver and enhanced intracellular domain MRP2 internalization. Notably, expression of miR-128-3p, a potential biomarker of estrogen-related cholestasis discovered by the authors, was significantly elevated. It was demonstrated that miR-128-3p targeted the 3\u2019-untranslated region of PDZK1 in EIC and consequently promoted MRP2 internalization.<\/p>\n

Accordingly, miR-128-3p suppression upregulated PDZK1, thereby suppressing MRP2 internalization and significantly attenuating cholestatic liver disease. Furthermore, MRP2 internalization and PDZK1 downregulation, as well as excessive miR-128-3p, in clinical samples from patients with cholestatic liver injury were observed.<\/p>\n

Overall, these findings illustrate that miR-128-3p inhibits PDZK1 expression, thereby inhibiting the membrane localization of MRP2 in EIC. Enhancing or restoring PDZK1 expression might therefore have therapeutic potential for cholestatic liver injury.<\/p>\n

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Yue Zu, Qianyan Gao and Yisheng He et al. MiR-128-3p mediates MRP2 internalization in estrogen-induced cholestasis through targeting PDZK1.\u00a0Acta Materia Medica.\u00a0<\/em>2025. Vol. 4(1):157-173. DOI: 10.15212\/AMM-2024-0053<\/p>\n","protected":false},"excerpt":{"rendered":"

Announcing a new publication for Acta Materia Medica journal. Estrogens have been reported to cause dysfunction in biliary transport systems, thereby inducing cholestasis. Multidrug resistance-associated protein 2 (MRP2) is a transporter responsible for independent bile flow. Emerging evidence indicates that PDZ domain containing 1 (PDZK1) regulates localization of MRP2; however, PDZK1\u2019s role and regulatory machinery […]<\/p>\n","protected":false},"author":5,"featured_media":1397,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[2],"tags":[408,103,409,410,411],"class_list":["post-1396","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news-and-events","tag-estrogen-induced-cholestasis","tag-localization","tag-mir-128-3p","tag-mrp2","tag-pdzk1"],"yoast_head":"\nMiR-128-3p mediates MRP2 internalization in estrogen-induced cholestasis through targeting PDZK1<\/title>\n<meta name=\"description\" content=\"miR-128-3p promotes MRP2 internalization by inhibiting PDZK1, contributing to estrogen-induced cholestasis. 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