{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T17:40:55Z","timestamp":1774374055057,"version":"3.50.1"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Mol Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Portal hypertension is critical to the development of ascites in liver cirrhosis. The aim of our study was to evaluate the contribution of portal hypertension to ascites formation and explore the underlying mechanism. Here, the role of portal hypertension in cirrhotic ascites was determined through a meta-analysis of portal pressure in cirrhotic patients and animal models. The mechanism underlying the involvement of portal hypertension in ascites formation was explored. The meta-analysis showed hepatic venous pressure gradient in patients with cirrhosis with ascites was significantly higher than that in patients with cirrhosis without ascites. In carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    )-treated rats, portal pressure of cirrhotic rats with ascites (19.83\u2009cmH\n                    <jats:sub>2<\/jats:sub>\n                    O) was significantly higher than that in cirrhotic rats without ascites (14.90\u2009cmH\n                    <jats:sub>2<\/jats:sub>\n                    O). In a novel murine model created by thioacetamide (TAA)\/CCl\n                    <jats:sub>4<\/jats:sub>\n                    administration plus partial portal vein ligation (PPVL), a significant increase in portal pressure and ascites amount was observed in the TAA\/CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2009+\u2009PPVL group compared with the TAA\/CCl\n                    <jats:sub>4<\/jats:sub>\n                    group. In the mice treated with TAA\/CCl\n                    <jats:sub>4<\/jats:sub>\n                    plus PPVL, the amount of ascites decreased significantly in mice with endothelial deletion of Piezo1 (Piezo1\n                    <jats:sup>\u25b3EC<\/jats:sup>\n                    ) compared with Piezo1\n                    <jats:sup>flox\/flox<\/jats:sup>\n                    mice. Finally, Piezo1 in liver sinusoidal endothelial cells and peritoneal endothelial cells promoted the development of portal hypertensive ascites via the nuclear factor kappa-B (NF-\u0138B)\u2212aquaporin1 (AQP1) pathway. In conclusion, Piezo1 in endothelium contributes to the formation of portal hypertensive ascites via the NF-\u0138B\u2212AQP1 pathway in liver cirrhosis, which indicates that blockage of the Piezo1\u2212NF\u0138B\u2212AQP1 pathway may be a useful strategy for the management of ascites in liver cirrhosis.\n                  <\/jats:p>","DOI":"10.1038\/s12276-025-01554-6","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T06:14:44Z","timestamp":1759299284000},"page":"2305-2316","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Portal hypertension contributes to ascites formation via the Piezo1\u2212nuclear factor kappa-B\u2212aquaporin1 pathway in liver cirrhosis"],"prefix":"10.1038","volume":"57","author":[{"given":"Ning","family":"Wei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuanglong","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangyang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haonan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengbo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohua","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4178-4916","authenticated-orcid":false,"given":"Yuhu","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"1554_CR1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/apt.15042","volume":"49","author":"L Du","year":"2019","unstructured":"Du, L. et al. Ascitic cholesterol is superior to serum-ascites albumin gradient in the detection of non-portal hypertensive ascites and the diagnosis of mixed ascites. Aliment. Pharm. Ther. 49, 91\u201398 (2019).","journal-title":"Aliment. Pharm. Ther."},{"key":"1554_CR2","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/jgh.14768","volume":"35","author":"S Zhu","year":"2020","unstructured":"Zhu, S. et al. Ascitic fluid total protein, a useful marker in non-portal hypertensive ascites. J. Gastroenterol. Hepatol. 35, 271\u2013277 (2020).","journal-title":"J. Gastroenterol. Hepatol."},{"key":"1554_CR3","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1136\/gutjnl-2020-321790","volume":"70","author":"GP Aithal","year":"2021","unstructured":"Aithal, G. P. et al. Guidelines on the management of ascites in cirrhosis. Gut, 70, 9\u201329 (2021).","journal-title":"Gut"},{"key":"1554_CR4","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1002\/hep.31884","volume":"74","author":"SW Biggins","year":"2021","unstructured":"Biggins, S. W. et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 74, 1014\u20131048 (2021).","journal-title":"Hepatology"},{"key":"1554_CR5","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1055\/s-0039-3399502","volume":"40","author":"N Kang","year":"2020","unstructured":"Kang, N. Mechanotransduction in liver diseases. Semin. Liver Dis. 40, 84\u201390 (2020).","journal-title":"Semin. Liver Dis."},{"key":"1554_CR6","volume":"5","author":"E Felli","year":"2023","unstructured":"Felli, E. et al. Mechanobiology of portal hypertension. JHEP Rep. 5, 100869 (2023).","journal-title":"JHEP Rep."},{"key":"1554_CR7","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1016\/j.jhep.2022.08.028","volume":"77","author":"EK Mitten","year":"2022","unstructured":"Mitten, E. K. & Baffy, G. Mechanotransduction in the pathogenesis of non-alcoholic fatty liver disease. J. Hepatol. 77, 1642\u20131656 (2022).","journal-title":"J. Hepatol."},{"key":"1554_CR8","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1146\/annurev-physiol-060721-100935","volume":"84","author":"K Poole","year":"2022","unstructured":"Poole, K. The diverse physiological functions of mechanically activated ion channels in mammals. Annu. Rev. Physiol. 84, 307\u2013329 (2022).","journal-title":"Annu. Rev. Physiol."},{"key":"1554_CR9","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.tips.2019.10.002","volume":"40","author":"D Douguet","year":"2019","unstructured":"Douguet, D., Patel, A., Xu, A., Vanhoutte, P. M. & Honor\u00e9, E. Piezo ion channels in cardiovascular mechanobiology. Trends Pharm. Sci. 40, 956\u2013970 (2019).","journal-title":"Trends Pharm. Sci."},{"key":"1554_CR10","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1016\/j.gendis.2022.08.015","volume":"10","author":"J Huang","year":"2023","unstructured":"Huang, J. et al. The Janus-faced role of Piezo1 in cardiovascular health under mechanical stimulation. Genes Dis. 10, 1956\u20131968 (2023).","journal-title":"Genes Dis."},{"key":"1554_CR11","doi-asserted-by":"crossref","first-page":"12980","DOI":"10.1073\/pnas.1902165116","volume":"116","author":"EE Friedrich","year":"2019","unstructured":"Friedrich, E. E. et al. Endothelial cell Piezo1 mediates pressure-induced lung vascular hyperpermeability via disruption of adherens junctions. Proc. Natl Acad. Sci. USA 116, 12980\u201312985 (2019).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1554_CR12","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jhep.2016.07.009","volume":"66","author":"J Poisson","year":"2017","unstructured":"Poisson, J. et al. Liver sinusoidal endothelial cells: physiology and role in liver diseases. J. Hepatol. 66, 212\u2013227 (2017).","journal-title":"J. Hepatol."},{"key":"1554_CR13","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/nature09002","volume":"465","author":"Y Wang","year":"2010","unstructured":"Wang, Y. et al. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature 465, 483\u2013486 (2010).","journal-title":"Nature"},{"key":"1554_CR14","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/hep.24418","volume":"54","author":"A Berzigotti","year":"2011","unstructured":"Berzigotti, A. et al. Obesity is an independent risk factor for clinical decompensation in patients with cirrhosis. Hepatology 54, 555\u2013561 (2011).","journal-title":"Hepatology"},{"key":"1554_CR15","doi-asserted-by":"crossref","first-page":"5280","DOI":"10.1007\/s10620-021-07334-2","volume":"67","author":"A Jindal","year":"2022","unstructured":"Jindal, A., Sarin, S. K., Kumar, M. & Kumar, G. Clinical outcomes in patients with advanced chronic liver disease and hepatic venous pressure gradient\u2009\u2264\u200910 mm Hg. Dig. Dis. Sci. 67, 5280\u20135289 (2022).","journal-title":"Dig. Dis. Sci."},{"key":"1554_CR16","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1111\/liv.12539","volume":"34","author":"D Rinc\u00f3n","year":"2014","unstructured":"Rinc\u00f3n, D. et al. Oral probiotic VSL#3 attenuates the circulatory disturbances of patients with cirrhosis and ascites. Liver Int. 34, 1504\u20131512 (2014).","journal-title":"Liver Int."},{"key":"1554_CR17","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1053\/gast.1997.v113.pm9247479","volume":"113","author":"L Ruiz-del-Arbol","year":"1997","unstructured":"Ruiz-del-Arbol, L. et al. Paracentesis-induced circulatory dysfunction: mechanism and effect on hepatic hemodynamics in cirrhosis. Gastroenterology 113, 579\u2013586 (1997).","journal-title":"Gastroenterology"},{"key":"1554_CR18","first-page":"753","volume":"22","author":"A Luca","year":"1995","unstructured":"Luca, A. et al. Beneficial effects of intravenous albumin infusion on the hemodynamic and humoral changes after total paracentesis. Hepatology 22, 753\u2013758 (1995).","journal-title":"Hepatology"},{"key":"1554_CR19","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/hep.1840070129","volume":"7","author":"R Moreau","year":"1987","unstructured":"Moreau, R., Lee, S. S., Hadengue, A., Braillon, A. & Lebrec, D. Hemodynamic effects of a clonidine-induced decrease in sympathetic tone in patients with cirrhosis. Hepatology 7, 149\u2013154 (1987).","journal-title":"Hepatology"},{"key":"1554_CR20","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/hep.1840130116","volume":"13","author":"A Hadengue","year":"1991","unstructured":"Hadengue, A. et al. Selective dopamine DA1 stimulation with fenoldopam in cirrhotic patients with ascites: a systemic, splanchnic and renal hemodynamic study. Hepatology 13, 111\u2013116 (1991).","journal-title":"Hepatology"},{"key":"1554_CR21","first-page":"30","volume":"20","author":"A Luca","year":"1994","unstructured":"Luca, A. et al. Favorable effects of total paracentesis on splanchnic hemodynamics in cirrhotic patients with tense ascites. Hepatology 20, 30\u201333 (1994).","journal-title":"Hepatology"},{"key":"1554_CR22","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/ajg.2011.456","volume":"107","author":"V Hern\u00e1ndez-Gea","year":"2012","unstructured":"Hern\u00e1ndez-Gea, V. et al. Development of ascites in compensated cirrhosis with severe portal hypertension treated with \u03b2-blockers. Am. J. Gastroenterol. 107, 418\u2013427 (2012).","journal-title":"Am. J. Gastroenterol."},{"key":"1554_CR23","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1007\/s10620-006-9310-2","volume":"51","author":"M Wadhawan","year":"2006","unstructured":"Wadhawan, M., Dubey, S., Sharma, B. C., Sarin, S. K. & Sarin, S. K. Hepatic venous pressure gradient in cirrhosis: correlation with the size of varices, bleeding, ascites, and child\u2019s status. Dig. Dis. Sci. 51, 2264\u20132269 (2006).","journal-title":"Dig. Dis. Sci."},{"key":"1554_CR24","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s12664-009-0019-y","volume":"28","author":"GM Gulzar","year":"2009","unstructured":"Gulzar, G. M. et al. Correlation of hepatic venous pressure gradient with variceal bleeding, size of esophageal varices, etiology, ascites and degree of liver dysfunction in cirrhosis of liver. Indian J. Gastroenterol. 28, 59\u201361 (2009).","journal-title":"Indian J. Gastroenterol."},{"key":"1554_CR25","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1111\/j.1440-1746.2009.05873.x","volume":"24","author":"Y Narahara","year":"2009","unstructured":"Narahara, Y. et al. Effects of terlipressin on systemic, hepatic and renal hemodynamics in patients with cirrhosis. J. Gastroenterol. Hepatol. 24, 1791\u20131797 (2009).","journal-title":"J. Gastroenterol. Hepatol."},{"key":"1554_CR26","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.jhep.2017.12.027","volume":"68","author":"L Turco","year":"2018","unstructured":"Turco, L. et al. Cardiopulmonary hemodynamics and C-reactive protein as prognostic indicators in compensated and decompensated cirrhosis. J. Hepatol. 68, 949\u2013958 (2018).","journal-title":"J. Hepatol."},{"key":"1554_CR27","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/00042737-200103000-00006","volume":"13","author":"I Colle","year":"2001","unstructured":"Colle, I. et al. Relationships between haemodynamic alterations and the development of ascites or refractory ascites in patients with cirrhosis. Eur. J. Gastroenterol. Hepatol. 13, 251\u2013256 (2001).","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"1554_CR28","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1046\/j.1440-1746.2003.03144.x","volume":"18","author":"YY Yang","year":"2003","unstructured":"Yang, Y. Y. et al. Plasma erythropoietin level in patients with cirrhosis and its relationship to the severity of cirrhosis and renal function. J. Gastroenterol. Hepatol. 18, 1156\u20131161 (2003).","journal-title":"J. Gastroenterol. Hepatol."},{"key":"1554_CR29","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1046\/j.1440-1746.1999.01853.x","volume":"14","author":"WC Lee","year":"1999","unstructured":"Lee, W. C. et al. Effect of anaemia on haemodynamics in patients with cirrhosis. J. Gastroenterol. Hepatol. 14, 370\u2013375 (1999).","journal-title":"J. Gastroenterol. Hepatol."},{"key":"1554_CR30","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1159\/000187513","volume":"65","author":"R Moreau","year":"1993","unstructured":"Moreau, R. et al. Renal hemodynamics in patients with cirrhosis: relationship with ascites and liver failure. Nephron 65, 359\u2013363 (1993).","journal-title":"Nephron"},{"key":"1554_CR31","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/j.1440-1746.1994.tb01235.x","volume":"9","author":"HC Meng","year":"1994","unstructured":"Meng, H. C. et al. Relationships between the severity of cirrhosis and haemodynamic values in patients with cirrhosis. J. Gastroenterol. Hepatol. 9, 148\u2013153 (1994).","journal-title":"J. Gastroenterol. Hepatol."},{"key":"1554_CR32","volume":"1870","author":"N Wei","year":"2024","unstructured":"Wei, N. et al. Hypoalbuminemia contributes to ascites formation via sodium and water retention: evidence from clinical date and albumin deficient mice. Biochim. Biophys. Acta Mol. Basis Dis. 1870, 167275 (2024).","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"1554_CR33","volume":"3","author":"Y Iwakiri","year":"2021","unstructured":"Iwakiri, Y. & Trebicka, J. Portal hypertension in cirrhosis: pathophysiological mechanisms and therapy. JHEP Rep. 3, 100316 (2021).","journal-title":"JHEP Rep."},{"key":"1554_CR34","first-page":"535","volume":"41","author":"JB Gibson","year":"1962","unstructured":"Gibson, J. B. & Smith, J. C. The origin of ascites in experimental cirrhosis in the rat. Am. J. Pathol. 41, 535\u2013547 (1962).","journal-title":"Am. J. Pathol."},{"key":"1554_CR35","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1038\/sj.ki.5000285","volume":"69","author":"J Ni","year":"2006","unstructured":"Ni, J. et al. Aquaporin-1 plays an essential role in water permeability and ultrafiltration during peritoneal dialysis. Kidney Int. 69, 1518\u20131525 (2006).","journal-title":"Kidney Int."},{"key":"1554_CR36","doi-asserted-by":"crossref","first-page":"C76","DOI":"10.1152\/ajpcell.1999.276.1.C76","volume":"276","author":"B Yang","year":"1999","unstructured":"Yang, B. et al. Reduced osmotic water permeability of the peritoneal barrier in aquaporin-1 knockout mice. Am. J. Physiol. 276, C76\u2013C81 (1999).","journal-title":"Am. J. Physiol."},{"key":"1554_CR37","doi-asserted-by":"crossref","first-page":"e0145513","DOI":"10.1371\/journal.pone.0145513","volume":"11","author":"W Zhang","year":"2016","unstructured":"Zhang, W. et al. Novel endothelial cell-specific AQP1 knockout mice confirm the crucial role of endothelial AQP1 in ultrafiltration during peritoneal dialysis. PLoS ONE 11, e0145513 (2016).","journal-title":"PLoS ONE"},{"key":"1554_CR38","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/ki.2013.250","volume":"85","author":"O Devuyst","year":"2014","unstructured":"Devuyst, O. & Rippe, B. Water transport across the peritoneal membrane. Kidney Int. 85, 750\u2013758 (2014).","journal-title":"Kidney Int."},{"key":"1554_CR39","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1016\/j.ymthe.2022.05.021","volume":"30","author":"J Wu","year":"2022","unstructured":"Wu, J. et al. Self-amplifying loop of NF-\u03baB and periostin initiated by PIEZO1 accelerates mechano-induced senescence of nucleus pulposus cells and intervertebral disc degeneration. Mol. Ther. 30, 3241\u20133256 (2022).","journal-title":"Mol. Ther."},{"key":"1554_CR40","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.jhep.2009.09.008","volume":"51","author":"M Domenicali","year":"2009","unstructured":"Domenicali, M. et al. A novel model of CCl4-induced cirrhosis with ascites in the mouse. J. Hepatol. 51, 991\u2013999 (2009).","journal-title":"J. Hepatol."},{"key":"1554_CR41","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1111\/j.1478-3231.2011.02610.x","volume":"31","author":"H Yokomori","year":"2011","unstructured":"Yokomori, H., Oda, M., Yoshimura, K., Kaneko, F. & Hibi, T. Aquaporin-1 associated with hepatic arterial capillary proliferation on hepatic sinusoid in human cirrhotic liver. Liver Int. 31, 1554\u20131564 (2011).","journal-title":"Liver Int."},{"key":"1554_CR42","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/hep.23628","volume":"52","author":"RC Huebert","year":"2010","unstructured":"Huebert, R. C. et al. Aquaporin-1 facilitates angiogenic invasion in the pathological neovasculature that accompanies cirrhosis. Hepatology 52, 238\u2013248 (2010).","journal-title":"Hepatology"},{"key":"1554_CR43","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.bbadis.2018.07.018","volume":"1865","author":"P K\u00f6nigshofer","year":"2019","unstructured":"K\u00f6nigshofer, P., Brusilovskaya, K., Schwabl, P. & Reiberger, T. Animal models of portal hypertension. Biochim. Biophys. Acta Mol. Basis Dis. 1865, 1019\u20131030 (2019).","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"1554_CR44","volume":"5","author":"F Wong","year":"2023","unstructured":"Wong, F. Innovative approaches to the management of ascites in cirrhosis. JHEP Rep. 5, 100749 (2023).","journal-title":"JHEP Rep."},{"key":"1554_CR45","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.jhep.2018.03.024","volume":"69","author":"European Association for the Study of the Liver","year":"2018","unstructured":"European Association for the Study of the Liver EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J. Hepatol. 69, 406\u2013460 (2018).","journal-title":"J. Hepatol."},{"key":"1554_CR46","doi-asserted-by":"crossref","first-page":"H1051","DOI":"10.1152\/ajpheart.00499.2014","volume":"308","author":"T Nguyen","year":"2015","unstructured":"Nguyen, T. et al. Aquaporin-1 facilitates pressure-driven water flow across the aortic endothelium. Am. J. Physiol. Heart Circ. Physiol. 308, H1051\u2013H1064 (2015).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"1554_CR47","doi-asserted-by":"crossref","first-page":"H1063","DOI":"10.1152\/ajpheart.00651.2016","volume":"313","author":"J Toussaint","year":"2017","unstructured":"Toussaint, J. et al. Chronic hypertension increases aortic endothelial hydraulic conductivity by upregulating endothelial aquaporin-1 expression. Am. J. Physiol. Heart Circ. Physiol. 313, H1063\u2013h1073 (2017).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"1554_CR48","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1002\/hep.21414","volume":"44","author":"C Esteva-Font","year":"2006","unstructured":"Esteva-Font, C. et al. Aquaporin-1 and aquaporin-2 urinary excretion in cirrhosis: Relationship with ascites and hepatorenal syndrome. Hepatology 44, 1555\u20131563 (2006).","journal-title":"Hepatology"},{"key":"1554_CR49","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.prp.2009.06.014","volume":"205","author":"ZH Xian","year":"2009","unstructured":"Xian, Z. H., Cong, W. M., Wang, Y. H., Wang, B. & Wu, M. C. Expression and localization of aquaporin-1 in human cirrhotic liver. Pathol. Res. Pract. 205, 774\u2013780 (2009).","journal-title":"Pathol. Res. Pract."},{"key":"1554_CR50","doi-asserted-by":"crossref","first-page":"11105","DOI":"10.1074\/jbc.M116.724690","volume":"291","author":"K Udwan","year":"2016","unstructured":"Udwan, K. et al. Oxidative stress and nuclear factor \u03baB (NF-\u03baB) increase peritoneal filtration and contribute to ascites formation in nephrotic syndrome. J. Biol. Chem. 291, 11105\u201311113 (2016).","journal-title":"J. Biol. Chem."},{"key":"1554_CR51","volume":"2022","author":"RZ Zhang","year":"2022","unstructured":"Zhang, R. Z., Liu, Y., Li, M., Huang, Y. L. & Song, Z. H. Qi Sui Zhu Shui plaster inhibits AQP1 and MAPK signaling reduces liver damage induced by cirrhotic ascites. J. Health. Eng. 2022, 9928546 (2022).","journal-title":"J. Health. Eng."},{"key":"1554_CR52","doi-asserted-by":"crossref","unstructured":"Chung, C. & Iwakiri, Y. The lymphatic vascular system in liver diseases: its role in ascites formation. Clin. Mol. Hepatol. 19, 99\u2013104 (2013).","DOI":"10.3350\/cmh.2013.19.2.99"},{"key":"1554_CR53","doi-asserted-by":"crossref","unstructured":"Juneja, P. et al. Recombinant VEGF-C (Cys156Ser) improves mesenteric lymphatic drainage and gut immune surveillance in experimental cirrhosis. JHEP Rep. 5, 100816 (2023).","DOI":"10.1016\/j.jhepr.2023.100816"},{"key":"1554_CR54","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1136\/gutjnl-2011-300703","volume":"62","author":"J Ribera","year":"2013","unstructured":"Ribera, J. et al. Increased nitric oxide production in lymphatic endothelial cells causes impairment of lymphatic drainage in cirrhotic rats. Gut. 62, 138\u2013145 (2013).","journal-title":"Gut"}],"container-title":["Experimental &amp; Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s12276-025-01554-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s12276-025-01554-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s12276-025-01554-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T23:04:14Z","timestamp":1762297454000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s12276-025-01554-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":54,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["1554"],"URL":"https:\/\/doi.org\/10.1038\/s12276-025-01554-6","relation":{},"ISSN":["2092-6413"],"issn-type":[{"value":"2092-6413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]},"assertion":[{"value":"31 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 July 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}