{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:25:27Z","timestamp":1782822327979,"version":"3.54.5"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":39,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"crossref","award":["22-14-00152-P"],"award-info":[{"award-number":["22-14-00152-P"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Clinical and experimental findings indicate that splenectomy stimulates liver regeneration. The mechanisms of this effect are uncertain. This study aimed to assess the effect of splenectomy on the state of sinusoidal endothelial cells during liver regeneration after 70% resection in mouse model. Two series of experiments were performed. In the first series, splenectomy was performed on sexually mature male C57BL\/6 mice, followed by 70% liver resection 7\u00a0days later. In the second series, only 70% liver resection was performed. The animals were withdrawn from the experiment 1, 3, or 7\u00a0days post-resection. The measurements encompassed the liver mass recovery dynamics; the AST, ALT, and albumin levels; and the proliferation activity of hepatocytes, as well as gene expression profiles, apoptosis rates, and proliferation activity of liver sinusoidal endothelial cells. Animals that underwent splenectomy before liver resection showed a decrease in the number of endothelial cells positive for VCAM-1 on days 1 and 7 post-resection and VE-cadherin-positive (CD144\u2009+) cells on day 7. Liver resection caused an increase in the relative counts of dying (Annexin-PI\u2009+) and Ki67\u2009+\u2009endothelial cells in the remnant. The apoptotic endothelial cell counts were significantly higher in the group with preserved spleen on day 1 post-resection, while the number of Ki67\u2009+\u2009endotheliocytes was higher in splenectomized animals on day 1 and day 3 post-resection. Splenectomy exerts significant effect on the state of endothelial cells of the sinusoidal capillaries of the regenerating liver. The gene expression profiling studied by microarray technology using Clariom\u2122 S Assay (mouse) revealed specific enrichment of the following signaling pathways in the endothelial cells of regenerating liver in splenectomized animals: PI3K-Akt-mTOR signaling pathway, Focal adhesion pathway, Chemokine signaling pathway. In this case, most of the differentially expressed genes were repressed. The decreased proinflammatory activation of sinusoidal endothelium results in decreased immigration of lymphocytes, notably CD3\u2009+\u2009\u0438 NK1.1 lymphocytes known to inhibit the regeneration. The results indicate that prior splenectomy mitigates the manifestation of shear stress in endothelial cells of the liver and reduces their pro-inflammatory activation, resulting in lower rates of migration of regeneration-inhibiting lymphocytes to the regenerating liver.<\/jats:p>","DOI":"10.1038\/s41598-025-32446-4","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T13:03:43Z","timestamp":1765631023000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Splenectomy reduces shear stress and inflammation in liver endothelial cells during regeneration after partial hepatectomy in mice"],"prefix":"10.1038","volume":"16","author":[{"given":"Andrey","family":"Elchaninov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Gantsova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Vishnyakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kuznetsova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Trofimov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timur","family":"Fatkhudinov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennady","family":"Sukhikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"32446_CR1","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41575-020-0342-4","volume":"18","author":"GK Michalopoulos","year":"2021","unstructured":"Michalopoulos, G. K. & Bhushan, B. Liver regeneration: Biological and pathological mechanisms and implications. Nat. Rev. Gastroenterol. Hepatol. 18, 40\u201355 (2021).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"32446_CR2","doi-asserted-by":"publisher","first-page":"2","DOI":"10.2353\/ajpath.2010.090675","volume":"176","author":"GK Michalopoulos","year":"2010","unstructured":"Michalopoulos, G. K. Liver Regeneration after Partial Hepatectomy. Am. J. Pathol. 176, 2\u201313 (2010).","journal-title":"Am. J. Pathol."},{"key":"32446_CR3","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1177\/0023677215572000","volume":"49","author":"Y Nevzorova","year":"2015","unstructured":"Nevzorova, Y., Tolba, R., Trautwein, C. & Liedtke, C. Partial hepatectomy in mice. Lab. Anim. 49, 81\u201388 (2015).","journal-title":"Lab. Anim."},{"key":"32446_CR4","doi-asserted-by":"publisher","first-page":"e30675","DOI":"10.1371\/journal.pone.0030675","volume":"7","author":"Y Zou","year":"2012","unstructured":"Zou, Y. et al. Four waves of hepatocyte proliferation linked with three waves of hepatic fat accumulation during partial hepatectomy-induced liver regeneration. PLoS ONE 7, e30675 (2012).","journal-title":"PLoS ONE"},{"key":"32446_CR5","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/s41575-021-00454-0","volume":"18","author":"GK Michalopoulos","year":"2021","unstructured":"Michalopoulos, G. K. Novel insights into liver homeostasis and regeneration. Nat. Rev. Gastroenterol. Hepatol. 18, 369\u2013370 (2021).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"issue":"276","key":"32446_CR6","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1126\/science.276.5309.60","volume":"1979","author":"GK Michalopoulos","year":"1997","unstructured":"Michalopoulos, G. K. & DeFrances, M. C. Liver regeneration. Science 1979(276), 60\u201366 (1997).","journal-title":"Science"},{"key":"32446_CR7","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s13619-021-00101-8","volume":"11","author":"W Pu","year":"2022","unstructured":"Pu, W. & Zhou, B. Hepatocyte generation in liver homeostasis, repair, and regeneration. Cell Regen. 11, 2 (2022).","journal-title":"Cell Regen."},{"key":"32446_CR8","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1007\/s00383-010-2660-z","volume":"26","author":"T Matsuura","year":"2010","unstructured":"Matsuura, T., Hayashida, M., Saeki, I. & Taguchi, T. The risk factors of persistent thrombocytopenia and splenomegaly after liver transplantation. Pediatr. Surg. Int. 26, 1007\u20131010 (2010).","journal-title":"Pediatr. Surg. Int."},{"key":"32446_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.liver.2024.100210","volume":"14","author":"PM Parikh","year":"2024","unstructured":"Parikh, P. M. Thrombocytopenia and platelet dysfunction after transplant- evaluation, implication, and management. J. Liver Transplant. 14, 100210 (2024).","journal-title":"J. Liver Transplant."},{"key":"32446_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2021.105926","volume":"88","author":"L Wei","year":"2021","unstructured":"Wei, L. et al. Is simultaneous partial splenectomy during pediatric liver transplantation safe and effective for severe hypersplenism? A prospective cohort study. Int. J. Surg. 88, 105926 (2021).","journal-title":"Int. J. Surg."},{"key":"32446_CR11","doi-asserted-by":"publisher","first-page":"3534","DOI":"10.3748\/wjg.v19.i23.3534","volume":"19","author":"G Tarantino","year":"2013","unstructured":"Tarantino, G., Scalera, A. & Finelli, C. Liver-spleen axis: Intersection between immunity, infections and metabolism. World J. Gastroenterol. 19, 3534 (2013).","journal-title":"World J. Gastroenterol."},{"key":"32446_CR12","doi-asserted-by":"publisher","DOI":"10.5772\/INTECHOPEN.94337","author":"A Nugroho","year":"2020","unstructured":"Nugroho, A. Splenectomy in Liver Cirrhosis with Splenomegaly and Hypersplenism. Liver Pathol. https:\/\/doi.org\/10.5772\/INTECHOPEN.94337 (2020).","journal-title":"Liver Pathol."},{"key":"32446_CR13","volume-title":"Immunology of Processes of Adaptive Growth, Proliferation and Their Disorders","author":"AG Babaeva","year":"1987","unstructured":"Babaeva, A. G. & Zotikov, E. A. Immunology of Processes of Adaptive Growth, Proliferation and Their Disorders (Medicine, 1987)."},{"key":"32446_CR14","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.jhep.2020.08.017","volume":"74","author":"T Yoshizumi","year":"2021","unstructured":"Yoshizumi, T. et al. Simultaneous splenectomy improves outcomes after adult living donor liver transplantation. J. Hepatol. 74, 372\u2013379 (2021).","journal-title":"J. Hepatol."},{"key":"32446_CR15","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1111\/jgh.12316","volume":"28","author":"Y Arakawa","year":"2013","unstructured":"Arakawa, Y. et al. Effects of splenectomy on hepatic gene expression profiles after massive hepatectomy in rats. J. Gastroenterol. Hepatol. 28, 1669\u20131677 (2013).","journal-title":"J. Gastroenterol. Hepatol."},{"key":"32446_CR16","doi-asserted-by":"publisher","first-page":"626","DOI":"10.3390\/life12050626","volume":"12","author":"A Elchaninov","year":"2022","unstructured":"Elchaninov, A., Vishnyakova, P., Sukhikh, G. & Fatkhudinov, T. Spleen: Reparative regeneration and influence on liver. Life 12, 626 (2022).","journal-title":"Life"},{"key":"32446_CR17","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1111\/tri.12223","volume":"27","author":"T Yoichi","year":"2014","unstructured":"Yoichi, T. et al. Protective effects of simultaneous splenectomy on small-for-size liver graft injury in rat liver transplantation. Transpl. Int. 27, 106\u2013113 (2014).","journal-title":"Transpl. Int."},{"key":"32446_CR18","doi-asserted-by":"publisher","first-page":"1241819","DOI":"10.3389\/fcell.2023.1241819","volume":"11","author":"A Elchaninov","year":"2023","unstructured":"Elchaninov, A. et al. The spleen as a possible source of serine protease inhibitors and migrating monocytes required for liver regeneration after 70% resection in mice. Front. Cell Dev. Biol. 11, 1241819 (2023).","journal-title":"Front. Cell Dev. Biol."},{"key":"32446_CR19","doi-asserted-by":"publisher","first-page":"W168","DOI":"10.1093\/nar\/gkad393","volume":"51","author":"JE Evangelista","year":"2023","unstructured":"Evangelista, J. E. et al. Enrichr-KG: Bridging enrichment analysis across multiple libraries. Nucleic Acids Res. 51, W168\u2013W179 (2023).","journal-title":"Nucleic Acids Res."},{"key":"32446_CR20","doi-asserted-by":"publisher","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":"32446_CR21","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1006\/niox.2001.0373","volume":"5","author":"JM Schoen","year":"2001","unstructured":"Schoen, J. M., Wang, H. H., Minuk, G. Y. & Lautt, W. W. Shear stress-induced nitric oxide release triggers the liver regeneration cascade. Nitric Oxide 5, 453\u2013464 (2001).","journal-title":"Nitric Oxide"},{"issue":"343","key":"32446_CR22","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1126\/science.1244880","volume":"1979","author":"J Hu","year":"2014","unstructured":"Hu, J. et al. Endothelial cell-derived Angiopoietin-2 controls liver regeneration as a spatiotemporal rheostat. Science 1979(343), 416\u2013419 (2014).","journal-title":"Science"},{"key":"32446_CR23","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/nature09493","volume":"468","author":"BS Ding","year":"2010","unstructured":"Ding, B. S. et al. Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration. Nature 468, 310\u2013315 (2010).","journal-title":"Nature"},{"key":"32446_CR24","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1038\/s12276-021-00574-2","volume":"53","author":"QS Liang","year":"2021","unstructured":"Liang, Q. S. et al. Splenectomy improves liver fibrosis via tumor necrosis factor superfamily 14 (LIGHT) through the JNK\/TGF-\u03b21 signaling pathway. Exp. Mol. Med. 53, 393\u2013406 (2021).","journal-title":"Exp. Mol. Med."},{"key":"32446_CR25","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1007\/s11605-012-2048-6","volume":"17","author":"N Golse","year":"2013","unstructured":"Golse, N. et al. New paradigms in post-hepatectomy liver failure. J. Gastrointest. Surg. 17, 593\u2013605. https:\/\/doi.org\/10.1007\/s11605-012-2048-6 (2013).","journal-title":"J. Gastrointest. Surg."},{"key":"32446_CR26","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1002\/bjs.9622","volume":"101","author":"H Kawanaka","year":"2014","unstructured":"Kawanaka, H. et al. Effect of laparoscopic splenectomy on portal haemodynamics in patients with liver cirrhosis and portal hypertension. Br. J. Surg. 101, 1585\u20131593 (2014).","journal-title":"Br. J. Surg."},{"key":"32446_CR27","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.advms.2022.02.005","volume":"67","author":"P Schwabl","year":"2022","unstructured":"Schwabl, P. et al. Splenectomy ameliorates portal pressure and anemia in animal models of cirrhotic and non-cirrhotic portal hypertension. Adv. Med. Sci. 67, 154\u2013162 (2022).","journal-title":"Adv. Med. Sci."},{"key":"32446_CR28","doi-asserted-by":"publisher","first-page":"5300","DOI":"10.1038\/s41467-018-07747-0","volume":"9","author":"T Izumi","year":"2018","unstructured":"Izumi, T. et al. Vagus-macrophage-hepatocyte link promotes post-injury liver regeneration and whole-body survival through hepatic FoxM1 activation. Nat. Commun. 9, 5300 (2018).","journal-title":"Nat. Commun."},{"key":"32446_CR29","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.semcdb.2017.07.041","volume":"71","author":"Z Song","year":"2017","unstructured":"Song, Z. et al. Mechanosensing in liver regeneration. Semin. Cell Dev. Biol. 71, 153\u2013167 (2017).","journal-title":"Semin. Cell Dev. Biol."},{"key":"32446_CR30","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/1423-0127-21-3","volume":"21","author":"H-J Hsieh","year":"2014","unstructured":"Hsieh, H.-J., Liu, C.-A., Huang, B., Tseng, A. H. & Wang, D. L. Shear-induced endothelial mechanotransduction: The interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications. J. Biomed. Sci. 21, 3 (2014).","journal-title":"J. Biomed. Sci."},{"key":"32446_CR31","doi-asserted-by":"publisher","first-page":"2390","DOI":"10.4049\/jimmunol.1600702","volume":"197","author":"Z Yao","year":"2016","unstructured":"Yao, Z. et al. Blood-Borne lipopolysaccharide is rapidly eliminated by liver sinusoidal endothelial cells via high-density lipoprotein. J. Immunol. 197, 2390\u20132399 (2016).","journal-title":"J. Immunol."},{"key":"32446_CR32","doi-asserted-by":"publisher","first-page":"4981","DOI":"10.4049\/jimmunol.1202017","volume":"189","author":"LP Ganesan","year":"2012","unstructured":"Ganesan, L. P. et al. Fc\u03b3RIIb on liver sinusoidal endothelium clears small immune complexes. J. Immunol. 189, 4981\u20134988 (2012).","journal-title":"J. Immunol."},{"key":"32446_CR33","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1038\/82161","volume":"6","author":"A Limmer","year":"2000","unstructured":"Limmer, A. et al. Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell tolerance. Nat. Med. 6, 1348\u20131354 (2000).","journal-title":"Nat. Med."},{"key":"32446_CR34","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1016\/j.jhep.2014.04.027","volume":"61","author":"A Carambia","year":"2014","unstructured":"Carambia, A. et al. TGF-\u03b2-dependent induction of CD4+CD25+Foxp3 + Tregs by liver sinusoidal endothelial cells. J. Hepatol. 61, 594\u2013599 (2014).","journal-title":"J. Hepatol."},{"key":"32446_CR35","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/j.jss.2013.03.033","volume":"184","author":"S Furuya","year":"2013","unstructured":"Furuya, S. et al. Interleukin-17A plays a pivotal role after partial hepatectomy in mice. J. Surg. Res. 184, 838\u2013846 (2013).","journal-title":"J. Surg. Res."},{"key":"32446_CR36","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1053\/j.gastro.2014.04.042","volume":"147","author":"R Rao","year":"2014","unstructured":"Rao, R. et al. Interleukin 17-producing \u03b3\u03b4T cells promote hepatic regeneration in mice. Gastroenterology 147, 473\u2013484 (2014).","journal-title":"Gastroenterology"},{"key":"32446_CR37","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.immuni.2013.07.018","volume":"39","author":"T Mchedlidze","year":"2013","unstructured":"Mchedlidze, T. et al. Interleukin-33-dependent innate lymphoid cells mediate hepatic fibrosis. Immunity 39, 357\u2013371 (2013).","journal-title":"Immunity"},{"issue":"312","key":"32446_CR38","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1126\/science.1121435","volume":"1979","author":"W Huang","year":"2006","unstructured":"Huang, W. et al. Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration. Science 1979(312), 233\u2013236 (2006).","journal-title":"Science"},{"key":"32446_CR39","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1002\/hep.27245","volume":"60","author":"J Bi","year":"2014","unstructured":"Bi, J. et al. TIGIT safeguards liver regeneration through regulating natural killer cell-hepatocyte crosstalk. Hepatology 60, 1389\u20131398 (2014).","journal-title":"Hepatology"},{"key":"32446_CR40","doi-asserted-by":"publisher","first-page":"1561815","DOI":"10.3389\/fcell.2025.1561815","volume":"13","author":"A Elchaninov","year":"2025","unstructured":"Elchaninov, A. et al. Cellular effects of splenectomy on liver regeneration after 70% resection. Front. Cell Dev. Biol. 13, 1561815 (2025).","journal-title":"Front. Cell Dev. Biol."},{"key":"32446_CR41","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.ijsu.2013.11.017","volume":"12","author":"EP Weledji","year":"2014","unstructured":"Weledji, E. P. Benefits and risks of splenectomy. Int. J. Surg. 12, 113\u2013119 (2014).","journal-title":"Int. J. Surg."},{"key":"32446_CR42","doi-asserted-by":"publisher","first-page":"392","DOI":"10.3324\/haematol.2013.092460","volume":"99","author":"SY Kristinsson","year":"2014","unstructured":"Kristinsson, S. Y., Gridley, G., Hoover, R. N., Check, D. & Landgren, O. Long-term risks after splenectomy among 8,149 cancer-free American veterans: A cohort study with up to 27 years follow-up. Haematologica 99, 392\u2013398 (2014).","journal-title":"Haematologica"},{"key":"32446_CR43","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1053\/jinf.2001.0904","volume":"43","author":"N Bisharat","year":"2001","unstructured":"Bisharat, N., Omari, H., Lavi, I. & Raz, R. Risk of infection and death among post-splenectomy patients. J. Infect. 43, 182\u2013186 (2001).","journal-title":"J. Infect."},{"key":"32446_CR44","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1002\/micr.20209","volume":"26","author":"S Sipka","year":"2006","unstructured":"Sipka, S. et al. Distribution of peripheral blood cells in mice after splenectomy or autotransplantation. Microsurgery 26, 43\u201349 (2006).","journal-title":"Microsurgery"},{"key":"32446_CR45","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.trim.2006.03.013","volume":"16","author":"S Sipka","year":"2006","unstructured":"Sipka, S. et al. Cellular and serological changes in the peripheral blood of splenectomized and spleen autotransplanted mice. Transpl. Immunol. 16, 99\u2013104 (2006).","journal-title":"Transpl. Immunol."},{"key":"32446_CR46","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1002\/micr.10166","volume":"23","author":"I Miko","year":"2003","unstructured":"Miko, I. et al. Hematological, hemorheological, immunological, and morphological studies of spleen autotransplantation in mice: Preliminary results. Microsurgery 23, 483\u2013488 (2003).","journal-title":"Microsurgery"},{"key":"32446_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12964-022-00918-z","volume":"20","author":"W Shu","year":"2022","unstructured":"Shu, W. et al. Cellular crosstalk during liver regeneration: Unity in diversity. Cell Commun. Signal. 20, 1\u201313 (2022).","journal-title":"Cell Commun. Signal."},{"key":"32446_CR48","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1016\/j.jhep.2015.07.002","volume":"63","author":"J Meyer","year":"2015","unstructured":"Meyer, J. et al. A focus on the role of platelets in liver regeneration: Do platelet-endothelial cell interactions initiate the regenerative process?. J. Hepatol. 63, 1263\u20131271. https:\/\/doi.org\/10.1016\/j.jhep.2015.07.002 (2015).","journal-title":"J. Hepatol."},{"key":"32446_CR49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059836","volume":"8","author":"K Nejak-Bowen","year":"2013","unstructured":"Nejak-Bowen, K., Orr, A., Bowen, W. C. & Michalopoulos, G. K. Conditional genetic elimination of hepatocyte growth factor in mice compromises liver regeneration after partial hepatectomy. PLoS ONE 8, e59836 (2013).","journal-title":"PLoS ONE"},{"key":"32446_CR50","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1002\/hep.24560","volume":"54","author":"Y Mei","year":"2011","unstructured":"Mei, Y. & Thevananther, S. Endothelial nitric oxide synthase is a key mediator of hepatocyte proliferation in response to partial hepatectomy in mice. Hepatology 54, 1777 (2011).","journal-title":"Hepatology"},{"key":"32446_CR51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0093304","volume":"9","author":"AP Palanisamy","year":"2014","unstructured":"Palanisamy, A. P. et al. Adenovirus-mediated eNOS expression augments liver injury after ischemia\/reperfusion in mice. PLoS ONE 9, e93304 (2014).","journal-title":"PLoS ONE"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32446-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32446-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32446-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T16:29:16Z","timestamp":1781627356000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32446-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,13]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["32446"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-32446-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,13]]},"assertion":[{"value":"6 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was conducted according to the guidelines \"The International Guiding Principles for Biomedical Research Involving Animals\" of 1985 and approved by the Institutional Review Board Board at the Avtsyn Research Institute of Human Morphology (Protocol No. 29 (5), November 8, 2021). This study is reported in accordance with the ARRIVE guidelines (PLoS Biol 8(6), e1000412, 2010) for animal research.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"2706"}}