{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T14:37:02Z","timestamp":1783953422529,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 109-2314-B-010-032-MY3"],"award-info":[{"award-number":["MOST 109-2314-B-010-032-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital","doi-asserted-by":"publisher","award":["V110-033"],"award-info":[{"award-number":["V110-033"]}],"id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In advanced cirrhosis, the TNF\u03b1-mediated intestinal inflammation and bacteria dysbiosis are involved in the development of inflammation and vasoconstriction-related renal dysfunction. In colitis and acute kidney injury models, activation of SIRT1 attenuates the TNF\u03b1-mediated intestinal and renal abnormalities. This study explores the impacts of intestinal SIRT1 deficiency and TNF\u03b1-mediated intestinal abnormalities on the development of cirrhosis-related renal dysfunction. Systemic and renal hemodynamics, intestinal dysbiosis [cirrhosis dysbiosis ratio (CDR) as marker of dysbiosis], and direct renal vasoconstrictive response (renal vascular resistance (RVR) and glomerular filtration rate (GFR)) to cumulative doses of TNF\u03b1 were measured in bile duct ligated (BDL)-cirrhotic ascitic mice. In SIRT1IEC-KO-BDL-ascitic mice, the worsening of intestinal dysbiosis exacerbates intestinal inflammation\/barrier dysfunction, the upregulation of the expressions of intestinal\/renal TNF\u03b1-related pathogenic signals, higher TNF\u03b1-induced increase in RVR, and decrease in GFR in perfused kidney. In intestinal SIRT1 knockout groups, the positive correlations were identified between intestinal SIRT1 activity and CDR. Particularly, the negative correlations were identified between CDR and RVR, with the positive correlation between CDR and GFR. In mice with advanced cirrhosis, the expression of intestinal SIRT1 is involved in the linkage between intestinal dysbiosis and vasoconstriction\/hypoperfusion-related renal dysfunction through the crosstalk between intestinal\/renal TNF\u03b1-related pathogenic inflammatory signals.<\/jats:p>","DOI":"10.3390\/ijms22031233","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T06:10:54Z","timestamp":1611727854000},"page":"1233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Intestinal SIRT1 Deficiency-Related Intestinal Inflammation and Dysbiosis Aggravate TNF\u03b1-Mediated Renal Dysfunction in Cirrhotic Ascitic Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Yu-Te","family":"Chou","sequence":"first","affiliation":[{"name":"Department of Medicine, Taipei Veterans General Hospital, Taipei 11267, Taiwan"},{"name":"Faculty of Medicine, School of Medicine, National 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