Abstract
Liver regeneration (LR) after partial hepatectomy (PH) requires the coordinate contribution of different cell types. Liver sinusoidal endothelial cells (LSECs), representing the largest population of nonparenchymal cells, are proven to be crucial in LR. However, the details about their implications in regeneration are not still clear. In this study, percoll density centrifugation and immunomagentic bead methods were used to isolate LSECs with high purity and yield; global transcriptional profiles of LSECs during the regeneration were investigated by microarray. 1,629 genes were identified to be LR-related. Among them, there were 833 known genes whose expression patterns were clustered into eight classes. Gene function enrichment analysis showed that genes involved in the major LSEC functions, i.e., coagulation, phagocytosis, and transport, were highly enriched in cluster characterized by rapid induction and gradual return, suggesting the quick reestablishment of LSEC function after PH. Genes in immunity/inflammation and defense response were enriched in clusters exhibiting transient downregulation and quick recovery, possibly being associated with suppression of immunity/inflammation pathway in LSECs at early phase. Genes in glycogen synthesis and glycolysis were enriched in the clusters marked by “significant increase and gradual return” and “slight increase and then downregulation”, implying an enhanced carbohydrate metabolism at early phase; detoxification-related genes were markedly distributed in the cluster with feature of rapid increase and then reduction, which was helpful in eliminating waste substance. Taken together, the measurement of gene expression profiling of LSECs and expression pattern analysis of functionally categorized genes gave insight into the mechanism of action of this cell on LR.
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References
Michalopoulos GK (2010) Liver regeneration after partial hepatectomy: critical analysis of mechanistic dilemmas. Am J Pathol 176:2–13
Zheng ZY, Weng SY, Yu Y (2009) Signal molecule-mediated hepatic cell communication during liver regeneration. World J Gastroenterol 15:5776–5783
** C, **aoling D, ** Z, Jiahong D, Jiming D, Lin Z (2006) Hepatic sinusoidal endothelial cells promote hepatocyte proliferation early after partial hepatectomy in rats. Arch Med Res 37:576–583
Malik R, Selden C, Hodgson H (2002) The role of non-parenchymal cells in liver growth. Semin Cell Dev Biol 13:425–431
March S, Hui EE, Underhill GH, Khetani S, Bhatia SN (2009) Microenvironmental regulation of the sinusoidal endothelial cell phenotype in vitro. Hepatology 50:920–928
Thiele GM, Duryee MJ, Freeman TL, Sorrell MF, Willis MS, Tuma DJ, Klassen LW (2005) Rat sinusoidal liver endothelial cells (SECs) produce pro-fibrotic factors in response to adducts formed from the metabolites of ethanol. Biochem Pharmacol 70:1593–1600
Ge X, Karrar A, Ericzon BG, Broomé U, Sumitran-Holgersson S (2005) Antibodies to liver sinusoidal endothelial cells modulate immune responses in liver transplantation. Transpl Proc 37:3335–3337
Seckert CK, Renzaho A, Tervo HM, Krause C, Deegen P, Kühnapfel B, Reddehase MJ, Grzimek NK (2009) Liver sinusoidal endothelial cells are a site of murine cytomegalovirus latency and reactivation. J Virol 83:8869–8884
Sato Y, Tsukada K, Hatakeyama K (1999) Role of shear stress and immune responses in liver regeneration after a partial hepatectomy. Surg Today 29:1–9
Wang WB, Fan JM, Zhang XL, Xu J, Yao W (2009) Serial expression analysis of liver regeneration-related genes in rat regenerating liver. Mol Biotechnol 43:221–231
Higgins GM, Anderson RM (1931) Experimental pathology of the liver: restoration of the liver of the white rat following partial surgical removal. Arch Pathol 12:186–202
Wang Z, Wang L, **e LF, Fan JY, Xu CS (2009) Isolation, purification and identification of sinusoidal endothelial cells in rat liver. Henna Sci 27:930–934
Gehring S, Sabo E, San Martin ME, Dickson EM, Cheng CW, Gregory SH (2009) Laser capture microdissection and genetic analysis of carbon-labeled Kupffer cells. World J Gastroenterol 15:1708–1718
Norton JN (1992) Total RNA isolation by a rapid centrifugation method. Am Biotechnol Lab 10:41
Scott RJ (1995) Isolation of whole cell (total) RNA. Methods Mol Biol 49:197–202
Kube DM, Savci-Hei**k CD, Lamblin AF, Kosari F, Vasmatzis G, Cheville JC, Klee GG (2007) Optimization of laser capture microdissection and RNA amplification for gene expression profiling of prostate cancer. BMC Mol Biol 8:25
Wang JZ, Du Z, Payattakool R, Yu PS, Chen CF (2007) A new method to measure the semantic similarity of GO terms. Bioinformatics 23:1274–1281
Guo WZ, Cai CP, Wang CB, Zhao L, Wang L, Zhang TZ (2008) A preliminary analysis of genome structure and composition in Gossypium hirsutum. BMC Genomics 9:314
Wang GP, Xu CS (2010) Reference gene selection for real-time rt-PCR in eight kinds of rat regenerating hepatic cells. Mol Biotechnol 46:49–57
Tashiro S (2009) Mechanism of liver regeneration after liver resection and portal vein embolization (ligation) is different? J Hepatobiliary Pancreat Surg 16:292–299
Macedo MP, Lautt WW (1996) Autoregulatory capacity in the superior mesenteric artery is attenuated by nitric oxide. Am J Physiol 271:G400–G404
Pelligrino DA, Wang Q, Koenig HM, Albrecht RF (1995) Role of nitric oxide, adenosine, N-methyl-d-aspartate receptors, and neuronal activation in hypoxia-induced pial arteriolar dilation in rats. Brain Res 704:61–70
Arii S, Imamura M (2000) Physiological role of sinusoidal endothelial cells and Kupffer cells and their implication in the pathogenesis of liver injury. J Hepatobiliary Pancreat Surg 7:40–48
Shovlin CL, Angus G, Manning RA, Okoli GN, Govani FS, Elderfield K, Birdsey GM, Mollet IG, Laffan MA, Mauri FA (2010) Endothelial cell processing and alternatively spliced transcripts of factor VIII: potential implications for coagulation cascades and pulmonary hypertension. PLoS One 5:e9154
Duryee MJ, Freeman TL, Willis MS, Hunter CD, Hamilton BC 3rd, Suzuki H, Tuma DJ, Klassen LW, Thiele GM (2005) Scavenger receptors on sinusoidal liver endothelial cells are involved in the uptake of aldehyde-modified proteins. Mol Pharmacol 68:1423–1430
Oie CI, Olsen R, Smedsrød B, Hansen JB (2008) Liver sinusoidal endothelial cells are the principal site for elimination of unfractionated heparin from the circulation. Am J Physiol Gastrointest Liver Physiol 294:G520–G528
Kindberg GM, Stang E, Andersen KJ, Roos N, Berg T (1990) Intracellular transport of endocytosed proteins in rat liver endothelial cells. Biochem J 270:205–211
Knolle PA, Limmer A (2003) Control of immune responses by savenger liver endothelial cells. Swiss Med Wkly 133:501–506
Limmer A, Knolle PA (2001) Liver sinusoidal endothelial cells: a new type of organ-resident antigen-presenting cell. Arch Immunol Ther Exp (Warsz) 49(l):S7–S11
Michalopoulos GK (2007) Liver regeneration. J Cell Physiol 213:286–300
Oda M (2004) Series introduction: hepatic sinusoidal cells in liver physiology and pathology. Med Electron Microsc 37:1–2
Su AI, Guidotti LG, Pezacki JP, Chisari FV, Schultz PG (2002) Gene expression during the priming phase of liver regeneration after partial hepatectomy in mice. Proc Natl Acad Sci USA 99:11181–11186
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This work was supported by the National Basic Research 973 Pre-research Program of China (No. 2010CB534905)
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Xu, Cs., Chen, Xg., Chang, Cf. et al. Analysis of time-course gene expression profiles of sinusoidal endothelial cells during liver regeneration in rats. Mol Cell Biochem 350, 215–227 (2011). https://doi.org/10.1007/s11010-010-0701-5
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DOI: https://doi.org/10.1007/s11010-010-0701-5