Skip to main content
Erschienen in: Digestive Diseases and Sciences 8/2006

01.08.2006 | Original Paper

Expression of Transforming Growth Factor-α and -β in Hepatic Lobes After Hemihepatic Portal Vein Embolization

verfasst von: Koji Kusaka, Hiroshi Imamura, Tomoaki Tomiya, Tadatoshi Takayama, Masatoshi Makuuchi

Erschienen in: Digestive Diseases and Sciences | Ausgabe 8/2006

Einloggen, um Zugang zu erhalten

Abstract

Hemihepatic portal vein embolization (PVE) concomitantly induces atrophy in embolized and compensatory hypertrophy in nonembolized hepatic lobes. The aim of the present study was to evaluate the involvement of growth stimulatory and inhibitory factors in these hepatic lobes after PVE. Liver specimens from the embolized and nonembolized lobes of ten patients who underwent hepatectomy (8–22 days) after undergoing PVE were obtained. Proliferation and apoptosis were examined immunohistochemically using Ki-67 and the Tdt-mediated dUTP-biotin nick end-labeling method. The expression of transforming growth factor-α (TGF-α) and transforming growth factor-β (TGF-β) was also examined by immunohistochemical staining. PVE induced hepatocyte apoptosis in the embolized lobe and hepatocyte proliferation in the nonembolized lobe. TGF-α expression in the hepatocytes of the nonembolized lobe was markedly increased, whereas TGF-α was also overexpressed, albeit moderately, in the embolized lobe. In contrast, TGF-β expression in the hepatocytes of the embolized lobe was significantly increased, and TGF-β expression was also increased, although to a lesser extent, in the nonembolized lobe. The degree of volume changes of the nonembolized lobe and the embolized lobe after PVE was statistically correlated with the ratios of TGF-α and TGF-β expression in these lobes (r = 0.886, P < .0001). In conclusion, these findings indicate that TGF-α and TGF-β expression (assessed by immunohistochemical staining) increase in relation to hepatocyte proliferation and apoptosis, respectively, after PVE in humans and the balance of the two factors may contribute to hepatic atrophy and hypertrophy concomitantly observed in this model.
Literatur
1.
Zurück zum Zitat Mead JE, Fausto N (1989) Transforming growth factor alpha may be a physiological regulator of liver regeneration by means of an autocrine mechanism. Proc Natl Acad Sci USA 86:1558–1562PubMedCrossRef Mead JE, Fausto N (1989) Transforming growth factor alpha may be a physiological regulator of liver regeneration by means of an autocrine mechanism. Proc Natl Acad Sci USA 86:1558–1562PubMedCrossRef
2.
Zurück zum Zitat Russel WE, Dempsey PJ, Sitaric S, Peck AJ, Coffey RJ Jr (1993) Transforming growth factor-α (TGFα) concentrations increase in regenerating rat liver: evidence for a delayed accumulation of murine TGFα. Endocrinology 133:1731–1738CrossRef Russel WE, Dempsey PJ, Sitaric S, Peck AJ, Coffey RJ Jr (1993) Transforming growth factor-α (TGFα) concentrations increase in regenerating rat liver: evidence for a delayed accumulation of murine TGFα. Endocrinology 133:1731–1738CrossRef
3.
Zurück zum Zitat Evarts RP, Nakatukasa H, Marsden ER, Hu Z, Thorgeirsson SS (1992) Expression of Transforming growth factor-α in regenerating liver and during hepatic differentiation. Mol Carcinog 5:25–31PubMed Evarts RP, Nakatukasa H, Marsden ER, Hu Z, Thorgeirsson SS (1992) Expression of Transforming growth factor-α in regenerating liver and during hepatic differentiation. Mol Carcinog 5:25–31PubMed
4.
Zurück zum Zitat Kinoshita T, Hirao S, Matsumoto K, Nakamura T (1991) Possible endocrine control of liver regeneration after partial hepatectomy. Biochem Biophys Res Commun 177:330–335PubMedCrossRef Kinoshita T, Hirao S, Matsumoto K, Nakamura T (1991) Possible endocrine control of liver regeneration after partial hepatectomy. Biochem Biophys Res Commun 177:330–335PubMedCrossRef
5.
Zurück zum Zitat Zarnegar R, DeFrances MC, Kost DP, Lindroos P, Michaloppoulos G (1991) Expression of hepatocyte growth factor mRNA in regenerating rat liver after partial hepatectomy. Biochem Biophys Res Commun 177:559–565PubMedCrossRef Zarnegar R, DeFrances MC, Kost DP, Lindroos P, Michaloppoulos G (1991) Expression of hepatocyte growth factor mRNA in regenerating rat liver after partial hepatectomy. Biochem Biophys Res Commun 177:559–565PubMedCrossRef
6.
Zurück zum Zitat Braun L, Mead JE, Panzica M, Mikumo R, Bell GI, Fausto N (1988) Transforming growth factor beta mRNA increases during liver regeneration; a possible paracrine mechanism of growth regulation. Proc Natl Acad Sci U S A 85:1539–1543PubMedCrossRef Braun L, Mead JE, Panzica M, Mikumo R, Bell GI, Fausto N (1988) Transforming growth factor beta mRNA increases during liver regeneration; a possible paracrine mechanism of growth regulation. Proc Natl Acad Sci U S A 85:1539–1543PubMedCrossRef
7.
Zurück zum Zitat Jakowlew SB, Mead JE, Danielpour D, Wu J, Roberts AB, Fausto N (1991) Transforming growth factor-β (TGF-β) isoforms in rat liver regeneration: messenger RNA expression and activation of latent TGF-β. Cell Regul 2:535–548PubMed Jakowlew SB, Mead JE, Danielpour D, Wu J, Roberts AB, Fausto N (1991) Transforming growth factor-β (TGF-β) isoforms in rat liver regeneration: messenger RNA expression and activation of latent TGF-β. Cell Regul 2:535–548PubMed
8.
Zurück zum Zitat Yasuda H, Mine T, Shibata H, Eto Y, Hasegawa Y, Takeuchi T, Asano S, et al. (1993) Activin A: an autocrine inhibitor of initiation of DNA synthesis in rat hepatocytes. J Clin Invest 92:1491–1496PubMedCrossRef Yasuda H, Mine T, Shibata H, Eto Y, Hasegawa Y, Takeuchi T, Asano S, et al. (1993) Activin A: an autocrine inhibitor of initiation of DNA synthesis in rat hepatocytes. J Clin Invest 92:1491–1496PubMedCrossRef
9.
Zurück zum Zitat Gandhi CR, Murase N, Subbotin VM, Uemura T, Nalesnik M, Demetris AJ, Fung JJ, et al. (2002) Portacaval shunt causes apoptosis and liver atrophy in rats despite increases in endogenous levels of major hepatic growth factors. J Hepatol 37:340–348PubMedCrossRef Gandhi CR, Murase N, Subbotin VM, Uemura T, Nalesnik M, Demetris AJ, Fung JJ, et al. (2002) Portacaval shunt causes apoptosis and liver atrophy in rats despite increases in endogenous levels of major hepatic growth factors. J Hepatol 37:340–348PubMedCrossRef
10.
Zurück zum Zitat Makuuchi M, Thai BL, Takayasu K, Takayama T, Kosuge T, Gunven P, Yamazaki S, et al. (1990) Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report. Surgery 107:521–527PubMed Makuuchi M, Thai BL, Takayasu K, Takayama T, Kosuge T, Gunven P, Yamazaki S, et al. (1990) Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report. Surgery 107:521–527PubMed
11.
Zurück zum Zitat Azoulay D, Raccuia JS, Castaing D, Bismuth H (1995) Right portal vein embolization in preparation for major hepatic resection. J Am Coll Surg 181:266–269PubMed Azoulay D, Raccuia JS, Castaing D, Bismuth H (1995) Right portal vein embolization in preparation for major hepatic resection. J Am Coll Surg 181:266–269PubMed
12.
Zurück zum Zitat Farges O, Belghiti J, Kianmanesh R, Regimbeau JM, Santoro R, Vilgrain V, Denys A, et al. (2003) Portal vein embolization before right hepatectomy: prospective clinical trial. Ann Surg 237:208–217PubMedCrossRef Farges O, Belghiti J, Kianmanesh R, Regimbeau JM, Santoro R, Vilgrain V, Denys A, et al. (2003) Portal vein embolization before right hepatectomy: prospective clinical trial. Ann Surg 237:208–217PubMedCrossRef
13.
Zurück zum Zitat Nagino M, Nimura Y, Kamiya J, Kondo S, Uesaka K, Kin Y, Hayakawa N, et al. (1995) Changes in hepatic lobe volume in biliary tract cancer patients after right portal vein embolization. Hepatology 21:434–439PubMed Nagino M, Nimura Y, Kamiya J, Kondo S, Uesaka K, Kin Y, Hayakawa N, et al. (1995) Changes in hepatic lobe volume in biliary tract cancer patients after right portal vein embolization. Hepatology 21:434–439PubMed
14.
Zurück zum Zitat Kubota K, Makuuchi M, Kusaka K, Kobayashi T, Miki K, Hesegawa K, Harihara Y, et al. (1997) Measurement of liver volume and hepatic functional reserve as a guide to decision-making in resectional surgery for hepatic tumors. Hepatology 26:1176–1181PubMed Kubota K, Makuuchi M, Kusaka K, Kobayashi T, Miki K, Hesegawa K, Harihara Y, et al. (1997) Measurement of liver volume and hepatic functional reserve as a guide to decision-making in resectional surgery for hepatic tumors. Hepatology 26:1176–1181PubMed
15.
Zurück zum Zitat Hui AM, Shi YZ, Li X, Sun L, Guido T, Takayama T, Makuuchi M (2002) Proliferative marker Ki-67 in gallbladder carcinomas: high expression level predicts early recurrence after surgical resection. Cancer Let. 176:191–198CrossRef Hui AM, Shi YZ, Li X, Sun L, Guido T, Takayama T, Makuuchi M (2002) Proliferative marker Ki-67 in gallbladder carcinomas: high expression level predicts early recurrence after surgical resection. Cancer Let. 176:191–198CrossRef
16.
Zurück zum Zitat Gravriedi Y (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119:493–501CrossRef Gravriedi Y (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119:493–501CrossRef
17.
Zurück zum Zitat Rous P, Larimore L (1920) Relation of the portal blood to liver maintenance. J Exp Med 31:609–632CrossRefPubMed Rous P, Larimore L (1920) Relation of the portal blood to liver maintenance. J Exp Med 31:609–632CrossRefPubMed
18.
Zurück zum Zitat Schalm L, Bax H, Mansens B (1956) Atrophy of the liver after occlusion of the bile ducts or portal vein and compensatory hypertrophy of the unoccluded portion and its clinical importance. Gastroenterology 31:131–155PubMed Schalm L, Bax H, Mansens B (1956) Atrophy of the liver after occlusion of the bile ducts or portal vein and compensatory hypertrophy of the unoccluded portion and its clinical importance. Gastroenterology 31:131–155PubMed
19.
Zurück zum Zitat Shimizu Y, Suzuki H, Nimura Y, Onoue S, Nagino M, Tanaka M, Ozawa T (1995) Elevated mitochondrial gene expression during rat liver regeneration after portal vein ligation. Hepatology 22:1222–1229PubMed Shimizu Y, Suzuki H, Nimura Y, Onoue S, Nagino M, Tanaka M, Ozawa T (1995) Elevated mitochondrial gene expression during rat liver regeneration after portal vein ligation. Hepatology 22:1222–1229PubMed
20.
Zurück zum Zitat Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715PubMed Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715PubMed
21.
Zurück zum Zitat Kamel OW, Franklin WA, Ringus JC, Meyer JS (1989) Thymidine labeling index and Ki-67 growth fraction in lesions of the breast. Am J Pathol 134:107–113PubMed Kamel OW, Franklin WA, Ringus JC, Meyer JS (1989) Thymidine labeling index and Ki-67 growth fraction in lesions of the breast. Am J Pathol 134:107–113PubMed
22.
Zurück zum Zitat Gerlach C, Sakkab DY, Scholzen T, Dassler R, Alison MR, Gerdes J (1997) Ki-67 expression during rat liver regeneration after partial hepatectomy. Hepatology 26:573–578PubMedCrossRef Gerlach C, Sakkab DY, Scholzen T, Dassler R, Alison MR, Gerdes J (1997) Ki-67 expression during rat liver regeneration after partial hepatectomy. Hepatology 26:573–578PubMedCrossRef
23.
Zurück zum Zitat Webber EM, FitzGerald MJ, Brown PI, Bartlett MH, Fausto N (1993) Transforming growth factor-alpha expression during liver regeneration after partial hepatectomy and toxic injury, and potential interactions between transforming growth factor-alpha and hepatocyte growth factor. Hepatology 18:1422–1431PubMedCrossRef Webber EM, FitzGerald MJ, Brown PI, Bartlett MH, Fausto N (1993) Transforming growth factor-alpha expression during liver regeneration after partial hepatectomy and toxic injury, and potential interactions between transforming growth factor-alpha and hepatocyte growth factor. Hepatology 18:1422–1431PubMedCrossRef
24.
Zurück zum Zitat Tomiya T, Ogata I, Fujiwara K (1998) Transforming growth factor α levels in liver and blood correlate better than hepatocyte growth factor with hepatocyte proliferation during liver regeneration. Am J Pathol 153:955–961PubMed Tomiya T, Ogata I, Fujiwara K (1998) Transforming growth factor α levels in liver and blood correlate better than hepatocyte growth factor with hepatocyte proliferation during liver regeneration. Am J Pathol 153:955–961PubMed
25.
Zurück zum Zitat Castilla A, Prieto J, Nelson F (1991) Transforming growth factors β1 and α in chronic liver disease. Effects of interferon alfa therapy. N Engl J Med 324:933–940PubMedCrossRef Castilla A, Prieto J, Nelson F (1991) Transforming growth factors β1 and α in chronic liver disease. Effects of interferon alfa therapy. N Engl J Med 324:933–940PubMedCrossRef
26.
Zurück zum Zitat Masuhara M, Yasunaga M, Tanigawa K, Tamura F, Yamashita S, Sakaida I, Okita K (1996) Expression of hepatocyte growth factor, transforming growth factor α, and transforming growth factor β1 messenger RNA in various human liver diseases and correlation with hepatocyte proliferation. Hepatology 24:323–329PubMed Masuhara M, Yasunaga M, Tanigawa K, Tamura F, Yamashita S, Sakaida I, Okita K (1996) Expression of hepatocyte growth factor, transforming growth factor α, and transforming growth factor β1 messenger RNA in various human liver diseases and correlation with hepatocyte proliferation. Hepatology 24:323–329PubMed
27.
Zurück zum Zitat Carr BI, Hayashi I, Branum EL, Moses HL (1986) Inhibition of DNA synthesis in rat hepatocytes by platelet-derived type β transforming growth factor. Cancer Res 46:2330–2334PubMed Carr BI, Hayashi I, Branum EL, Moses HL (1986) Inhibition of DNA synthesis in rat hepatocytes by platelet-derived type β transforming growth factor. Cancer Res 46:2330–2334PubMed
28.
Zurück zum Zitat Russel WE (1988) Transforming growth factor beta (TGF-β) inhibits hepatocyte DNA synthesis independently of EGF binding and EGF receptor autophosphorylation. J Cell Physiol 135:253–261CrossRef Russel WE (1988) Transforming growth factor beta (TGF-β) inhibits hepatocyte DNA synthesis independently of EGF binding and EGF receptor autophosphorylation. J Cell Physiol 135:253–261CrossRef
29.
Zurück zum Zitat Oberhammer F, Pavelka M, Sharma S, Tiefenbacher R, Purchio TA, Bursch W, Schulte-Hermann R (1992) Induction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor-beta1. Proc Natl Acad Sci U S A 89:5408–5412PubMedCrossRef Oberhammer F, Pavelka M, Sharma S, Tiefenbacher R, Purchio TA, Bursch W, Schulte-Hermann R (1992) Induction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor-beta1. Proc Natl Acad Sci U S A 89:5408–5412PubMedCrossRef
30.
Zurück zum Zitat Fukuda K, Kojiro M, Chiu J-F (1993) Induction of apoptosis by transforming growth factor-β1 in the rat hepatoma cell line McA-RH7777: a possible association with tissue transglutaminase expression. Hepatology 18:945–953PubMedCrossRef Fukuda K, Kojiro M, Chiu J-F (1993) Induction of apoptosis by transforming growth factor-β1 in the rat hepatoma cell line McA-RH7777: a possible association with tissue transglutaminase expression. Hepatology 18:945–953PubMedCrossRef
31.
Zurück zum Zitat Harada H, Imamura H, Miyagawa S, Kawasaki S (1997) Fate of the human liver after hemihepatic portal vein embolization: cell kinetic and morphometric study. Hepatology 26:1162–1170PubMed Harada H, Imamura H, Miyagawa S, Kawasaki S (1997) Fate of the human liver after hemihepatic portal vein embolization: cell kinetic and morphometric study. Hepatology 26:1162–1170PubMed
32.
Zurück zum Zitat Fang JW, Bird GL, Nakamura T, Davis GL, Lau JY (1994) Hepatocyte proliferation as an indicator of outcome in acute alcoholic hepatitis. Lancet 343:820–823PubMedCrossRef Fang JW, Bird GL, Nakamura T, Davis GL, Lau JY (1994) Hepatocyte proliferation as an indicator of outcome in acute alcoholic hepatitis. Lancet 343:820–823PubMedCrossRef
33.
Zurück zum Zitat Tu H, Jacobs SC, Borkowski A, Kyprianou N (1996) Incidence of apoptosis and cell proliferation in prostate cancer: relationship with TGF-beta1 and bcl-2 expression. Int J Cancer 69:357–363PubMedCrossRef Tu H, Jacobs SC, Borkowski A, Kyprianou N (1996) Incidence of apoptosis and cell proliferation in prostate cancer: relationship with TGF-beta1 and bcl-2 expression. Int J Cancer 69:357–363PubMedCrossRef
34.
Zurück zum Zitat Bissell DM, Wang SS, Jarnagin WR, Roll FJ (1995) Cell-specific expression of transforming growth factor-beta in rat liver. Evidence for autocrine regulation of hepatocyte proliferation. J Clin Invest 96:447–455PubMedCrossRef Bissell DM, Wang SS, Jarnagin WR, Roll FJ (1995) Cell-specific expression of transforming growth factor-beta in rat liver. Evidence for autocrine regulation of hepatocyte proliferation. J Clin Invest 96:447–455PubMedCrossRef
35.
Zurück zum Zitat Albright CD, Zeisel SH (1997) Choline deficiency causes increased localization of transforming growth factor-β1 signaling proteins and apoptosis in the rat liver. Pathobiology 65:264–270PubMedCrossRef Albright CD, Zeisel SH (1997) Choline deficiency causes increased localization of transforming growth factor-β1 signaling proteins and apoptosis in the rat liver. Pathobiology 65:264–270PubMedCrossRef
36.
Zurück zum Zitat Jirtle RL, Carr BI, Scott CD (1991) Modulation of insulin-like growth factor-II/mannose 6-phosphate receptors and transforming growth factor-beta 1 during liver regeneration. J Biol Chem 266:22444–22450PubMed Jirtle RL, Carr BI, Scott CD (1991) Modulation of insulin-like growth factor-II/mannose 6-phosphate receptors and transforming growth factor-beta 1 during liver regeneration. J Biol Chem 266:22444–22450PubMed
37.
Zurück zum Zitat Wada K, Nomura S, Morii E, Kitamura Y, Nishizawa Y, Miyake A, Terada N (1996) Changes in levels of mRNAs of transforming growth factor (TGF)-beta1, -beta2, -beta3, TGF-beta type II receptor and sulfated glycoprotein-2 during apoptosis of mouse uterine epithelium. J Steroid Biochem Mol Biol 59:367–375PubMedCrossRef Wada K, Nomura S, Morii E, Kitamura Y, Nishizawa Y, Miyake A, Terada N (1996) Changes in levels of mRNAs of transforming growth factor (TGF)-beta1, -beta2, -beta3, TGF-beta type II receptor and sulfated glycoprotein-2 during apoptosis of mouse uterine epithelium. J Steroid Biochem Mol Biol 59:367–375PubMedCrossRef
Metadaten
Titel
Expression of Transforming Growth Factor-α and -β in Hepatic Lobes After Hemihepatic Portal Vein Embolization
verfasst von
Koji Kusaka
Hiroshi Imamura
Tomoaki Tomiya
Tadatoshi Takayama
Masatoshi Makuuchi
Publikationsdatum
01.08.2006
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 8/2006
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-006-9105-5

Weitere Artikel der Ausgabe 8/2006

Digestive Diseases and Sciences 8/2006 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.