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Specifically, hepatocyte-intrinsic ER stress in cooperation with activated NRF2 leads to indirect activation of JNK-JUN signaling, which abrogates HNF1\u03b1-stimulated\n                    <jats:italic toggle=\"yes\">Fxr<\/jats:italic>\n                    gene transcription and reduces expression of the bile salt export pump BSEP. These signaling abnormalities, whose clinical relevance is supported by single cell transcriptomics of human PSC tissue, cause cholestasis, hepatocyte and bile canaliculi injury, biliary hyperplasia, and periductular fibrosis, which define PSC. Congruently, alleviation of cholestasis and\/or inhibition of biliary hyperplasia resolve PSC in mice.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2616211123","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:07:56Z","timestamp":1786464476000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Hepatocyte-intrinsic ER stress and NRF2 initiate primary sclerosing cholangitis, providing therapeutic insights"],"prefix":"10.1073","volume":"123","author":[{"given":"Lianyuan","family":"Tao","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03m1g2s55","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Metabolic and Liver Diseases, Sanford Burnham Prebys Medical Discovery Institute","place":["La Jolla"]},{"id":[{"id":"https:\/\/ror.org\/03t1yn780","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Hepatobiliary Surgery, The First Affiliated 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