Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-26T01:03:14.108Z Has data issue: false hasContentIssue false

Dynamics of Sept4 expression in fibrotic livers of mice infected with Schistosoma japonicum

Published online by Cambridge University Press:  17 June 2011

Y. N. DUAN*
Affiliation:
Department of Parasitology and Microbiology, School of Medicine, Nantong University; Nantong, Jiangsu Province, 226001, People's Republic of China
H. Y. QIAN
Affiliation:
Department of Parasitology and Microbiology, School of Medicine, Nantong University; Nantong, Jiangsu Province, 226001, People's Republic of China
Y. W. QIN
Affiliation:
Department of Parasitology and Microbiology, School of Medicine, Nantong University; Nantong, Jiangsu Province, 226001, People's Republic of China
D. D. ZHU
Affiliation:
Department of Parasitology and Microbiology, School of Medicine, Nantong University; Nantong, Jiangsu Province, 226001, People's Republic of China
X. X. HE
Affiliation:
Department of Parasitology and Microbiology, School of Medicine, Nantong University; Nantong, Jiangsu Province, 226001, People's Republic of China
Q. ZHOU
Affiliation:
Department of Parasitology and Microbiology, School of Medicine, Nantong University; Nantong, Jiangsu Province, 226001, People's Republic of China
Y. N. YANG
Affiliation:
Department of Parasitology and Microbiology, School of Medicine, Nantong University; Nantong, Jiangsu Province, 226001, People's Republic of China
J. BAO
Affiliation:
Department of Parasitology and Microbiology, School of Medicine, Nantong University; Nantong, Jiangsu Province, 226001, People's Republic of China
J. R. FENG
Affiliation:
Department of Parasitology and Microbiology, School of Medicine, Nantong University; Nantong, Jiangsu Province, 226001, People's Republic of China
W. SUN
Affiliation:
Department of Parasitology and Microbiology, School of Medicine, Nantong University; Nantong, Jiangsu Province, 226001, People's Republic of China
J. L. CHEN
Affiliation:
Department of Parasitology and Microbiology, School of Medicine, Nantong University; Nantong, Jiangsu Province, 226001, People's Republic of China
*
*Corresponding author: Tel: +86 513 85051738. E-mail: [email protected]

Summary

In order to investigate the dynamics of Septin4 (Sept4) expression and its function in the formation of fibrotic livers in mice infected with Schistosoma japonicum, we constructed the mouse model of S. japonicum egg-induced liver fibrosis for 24 weeks. Immunohistochemical staining, qRT-PCR and Western blot were used to detect the expression of Sept4 and α-smooth muscle actin (α-SMA). We found Sept4 localized in the perisinusoidal space where hepatic stellate cells (HSCs) distribute in the periphery of circumoval granulomas and the portal venule. The expression of Sept4 and α-SMA had a similar significant tendency of an up-regulation to a peak at 12 weeks post-infection (p.i.) followed by a down-regulation. At 24 weeks p.i. both were at a low level. These results suggest that Sept4 and α-SMA may interact together in HSCs. Based on this evidence, we hypothesize that Sept4 seems to be involved in the formation of inflammatory granulomata and subsequent liver fibrosis by regulating HSCs activation.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Arnaud, V., Li, J., Wang, Y., Fu, X., Mengzhi, S., Luo, X., Hou, X., Dessein, H., Jie, Z., Xin-Ling, Y., He, H., McManus, D. P., Li, Y. and Dessein, A. (2008). Regulatory role of interleukin-10 and interferon-gamma in severe hepatic central and peripheral fibrosis in humans infected with Schistosoma japonicum. Journal of Infectious Diseases 198(3), 418426. doi: 10.1086/588826.CrossRefGoogle Scholar
Bartley, P., Ramm, G., Jones, M., Ruddell, R., Li, Y. and McManus, D. (2006). A contributory role for activated hepatic stellate cells in the dynamics of Schistosoma japonicum egg-induced fibrosis. International Journal for Parasitology 36(9), 9931001. doi: 10.1016/j.ijpara.2006.04.015.CrossRefGoogle Scholar
Bataller, R. and Brenner, D. A. (2001). Hepatic stellate cells as a target for the treatment of liver fibrosis. Seminars in Liver Disease 21(3), 437451. doi: 10.1055/s-2001-17558.CrossRefGoogle Scholar
Burke, M. L., Jones, M. K., Gobert, G. N., Li, Y. S., Ellis, M. K. and McManus, D. P. (2009). Immunopathogenesis of human schistosomiasis. Parasite Immunology 31(4), 163176. doi: 10.1111/j.1365-3024.2009.01098.x.CrossRefGoogle Scholar
Carpino, G., Morini, S., Ginanni Corradini, S., Franchitto, A., Merli, M., Siciliano, M., Gentili, F., Onetti Muda, A., Berloco, P., Rossi, M., Attili, A. F. and Gaudio, E. (2005). Alpha-SMA expression in hepatic stellate cells and quantitative analysis of hepatic fibrosis in cirrhosis and in recurrent chronic hepatitis after liver transplantation. Digestive and Liver Disease 37(5), 349356. doi: 10.1016/j.dld.2004.11.009.CrossRefGoogle ScholarPubMed
Chang, K. T., Tsai, M. J., Cheng, Y. T., Chen, J. J., Hsia, R. H., Lo, Y. S., Ma, Y. R. and Weng, C. F. (2009). Comparative atomic force and scanning electron microscopy: an investigation of structural differentiation of hepatic stellate cells. Journal of Structural Biology 167(3), 200208. doi: 10.1016/j.jsb.2009.06.005.CrossRefGoogle Scholar
Chen, F., Cai, W., Chen, Z., Chen, X. and Liu, R. (2002). Dynamic changes in the collagen metabolism of liver fibrosis at the transcription level in rabbits with Schistosomiasis japonica. Chinese Medical Journal 115(11), 16371640.Google ScholarPubMed
De Minicis, S., Seki, E., Uchinami, H., Kluwe, J., Zhang, Y., Brenner, D. A. and Schwabe, R. F. (2007). Gene expression profiles during hepatic stellate cell activation in culture and in vivo. Gastroenterology 132(5), 19371946. doi: 10.1053/j.gastro.2007.02.033.CrossRefGoogle Scholar
Field, C. M. and Kellogg, D. (1999). Septins: cytoskeletal polymers or signalling GTPases? Trends in Cell Biology 9(10), 387394. doi: 10.1016/S0962-8924(99)01632-3.CrossRefGoogle ScholarPubMed
Friedman, S. L. (2000). Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. The Journal of Biological Chemistry 275(4), 22472250. doi: 10.1074/jbc.275.4.2247.CrossRefGoogle ScholarPubMed
Friedman, S. L. (2003). Liver fibrosis – from bench to bedside. Journal of Hepatology 38 (Suppl 1), S38S53. doi: 10.1016/S0168-8278(02)00429-4.CrossRefGoogle ScholarPubMed
Friedman, S. L. (2008). Hepatic fibrosis – overview. Toxicology 254(3), 120129. doi: 10.1016/j.tox.2008.06.013.CrossRefGoogle Scholar
Gottfried, Y., Rotem, A., Klein, E. and Larisch, S. (2007). The pro-apoptotic ARTS/Sept4 protein is significantly reduced in post-mortem brains from schizophrenic patients. Schizophrenia Research 96(1–3), 257266. doi: 10.1016/j.schres.2007.05.031.CrossRefGoogle ScholarPubMed
Ihara, M., Kinoshita, A., Yamada, S., Tanaka, H., Tanigaki, A., Kitano, A., Goto, M., Okubo, K., Nishiyama, H. and Ogawa, O. (2005). Cortical organization by the septin cytoskeleton Is essential for structural and mechanical integrity of mammalian spermatozoa. Developmental Cell 8(3), 343352. doi: 10.1016/j.devcel.2004.12.005.CrossRefGoogle ScholarPubMed
Iwaisako, K., Hatano, E., Taura, K., Nakajima, A., Tada, M., Seo, S., Tamaki, N., Sato, F., Ikai, I., Uemoto, S. and Kinoshita, M. (2008). Loss of Sept4 exacerbates liver fibrosis through the dysregulation of hepatic stellate cells. Journal of Hepatology 49(5), 768778. doi: 10.1016/j.jhep.2008.05.026.CrossRefGoogle ScholarPubMed
Kinoshita, A., Noda, M. and Kinoshita, M. (2000). Differential localization of septins in the mouse brain. The Journal of Comparative Neurology 428(2), 223239. doi: 10.1002/1096-9861(20001211)428:2<223::AID-CNE3>3.0.CO;2-M.3.0.CO;2-M>CrossRefGoogle Scholar
Kinoshita, M. (2006). Diversity of septin scaffolds. Current Opinion in Cell Biology 18(1), 5460. doi: 10.1016/j.ceb.2005.12.005.CrossRefGoogle Scholar
Kinoshita, M., Field, C. M., Coughlin, M. L., Straight, A. F. and Mitchison, T. J. (2002). Self- and actin-templated assembly of mammalian septins. Developmental Cell 3(6), 791802. doi: 10.1016/S1534-5807(02)00366-0.CrossRefGoogle ScholarPubMed
Kissel, H., Georgescu, M. M., Larisch, S., Manova, K., Hunnicutt, G. R. and Steller, H. (2005). The Sept4 septin locus is required for sperm terminal differentiation in mice. Developmental Cell 8(3) 353364. doi: 10.1016/j.devcel.2005.01.021.CrossRefGoogle Scholar
Kremer, B. E., Adang, L. A. and Macara, I. G. (2007). Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7. Cell 130(5), 837850. doi: 10.1016/j.cell.2007.06.053.CrossRefGoogle ScholarPubMed
Lindert, S., Wickert, L., Sawitza, I., Wiercinska, E., Gressner, A. M., Dooley, S. and Breitkopf, K. (2005). Transdifferentiation-dependent expression of alpha-SMA in hepatic stellate cells does not involve TGF-beta pathways leading to coinduction of collagen type I and thrombospondin-2. Matrix Biology 24(3), 198207. doi: 10.1016/j.matbio.2005.03.003.CrossRefGoogle Scholar
Spiliotis, E. T. (2006). Here come the septins: novel polymers that coordinate intracellular functions and organization. Journal of Cell Science 119(1), 410. doi: 10.1242/jcs.02746.CrossRefGoogle ScholarPubMed
Takeji, M., Moriyama, T., Oseto, S., Kawada, N., Hori, M., Imai, E. and Miwa, T. (2006). Smooth muscle alpha-actin deficiency in myofibroblasts leads to enhanced renal tissue fibrosis. The Journal of Biological Chemistry 281(52), 4019340200. doi: 10.1074/jbc.M602182200.CrossRefGoogle Scholar
Wilson, M. S., Mentink-Kane, M. M., Pesce, J. T., Ramalingam, T. R., Thompson, R. and Wynn, T. A. (2007). Immunopathology of schistosomiasis. Immunology and Cell Biology 85(2), 148154. doi: 10.1038/sj.icb.7100014.CrossRefGoogle ScholarPubMed
Wynn, T. A., Thompson, R. W., Cheever, A. W. and Mentink-Kane, M. M. (2004). Immunopathogenesis of schistosomiasis. Immunological Reviews 201, 156167. doi: 10.1111/j.0105-2896.2004.00176.x.CrossRefGoogle Scholar
Zhang, L. H., Pan, J. P., Yao, H. P., Sun, W. J., Xia, D. J., Wang, Q. Q., He, L., Wang, J. and Cao, X. (2001). Intrasplenic transplantation of IL-18 gene-modified hepatocytes: an effective approach to reverse hepatic fibrosis in schistosomiasis through induction of dominant Th1 response. Gene Therapy 8(17), 13331342. doi: 10.1038/sj.gt.3301524.CrossRefGoogle ScholarPubMed
Zieger, B., Tran, H., Hainmann, I., Wunderle, D., Zgaga-Griesz, A., Blaser, S. and Ware, J. (2000). Characterization and expression analysis of two human septin genes, PNUTL1 and PNUTL2. Gene 261(2), 197203. doi: 10.1016/S0378-1119(00)00527-8.CrossRefGoogle ScholarPubMed