Hepatic processing of transforming growth factor beta in the rat. Uptake, metabolism, and biliary excretion - PubMed (original) (raw)
- PMID: 3476497
- PMCID: PMC442299
- DOI: 10.1172/JCI113130
Hepatic processing of transforming growth factor beta in the rat. Uptake, metabolism, and biliary excretion
R J Coffey Jr et al. J Clin Invest. 1987 Sep.
Abstract
Transforming growth factor beta (TGF beta), a recently discovered polypeptide, modulates growth of normal and neoplastic cells. Since little is known concerning in vivo disposition of TGF beta, we performed studies to examine the hepatic processing of biologically active 125I-TGF beta in the rat. After intravenous injection, 125I-TGF beta disappeared from the plasma with an initial t1/2 of 2.2 min; partial hepatectomy delayed the plasma disappearance of 125I-TGF beta by 80%. 60 min after intrafemoral injection, 63% of the recovered label was present in liver and/or bile; by 90 min, most of the label removed by the liver (83%) had been slowly excreted into bile. Nearly all the label in bile (96%) was soluble in trichloracetic acid and not immunoprecipitable by specific antiserum. Colchicine and vinblastine inhibited cumulative biliary excretion of label by 28 and 37%, respectively; chloroquine and leupeptin each increased the amount of label in bile that was precipitable by trichloracetic acid and that coeluted with authentic 125I-TGF beta on molecular sieve chromatography. There was efficient first-pass hepatic extraction of 125I-TGF beta (36%) in the isolated perfused rat liver, which was inhibited by unlabeled TGF beta (but not by epidermal growth factor, EGF) and by lectins in a dose-dependent manner; prolonged fasting also decreased clearance (26%). After fractionation of liver by differential or isopycnic centrifugation, radiolabel codistributed with marker enzymes for lysosomes. The results indicate rapid, extensive, inhibitable, and organ-selective extraction of TGF beta by the liver. After extraction, TGF beta undergoes efficient transhepatic transport, extensive intracellular metabolism, and slow but complete biliary excretion of its metabolites. Liver fractionation studies and pharmacologic manipulations suggest that these processes are associated with organelles that include microtubules and lysosomes. The data suggest that the liver is a major target tissue or site of metabolism for biologically active TGF beta.
Similar articles
- Hepatectomy impairs hepatic processing of somatostatin-14.
Raper SE, Kothary PC, Kokudo N, DelValle J. Raper SE, et al. Am J Surg. 1993 Jan;165(1):89-94; discussion 94-5. doi: 10.1016/s0002-9610(05)80409-x. Am J Surg. 1993. PMID: 8093425 - Hepatic processing of cholecystokinin peptides. II. Cellular metabolism, transport, and biliary excretion.
Gores GJ, Miller LJ, LaRusso NF. Gores GJ, et al. Am J Physiol. 1986 Mar;250(3 Pt 1):G350-6. doi: 10.1152/ajpgi.1986.250.3.G350. Am J Physiol. 1986. PMID: 3953819 - Transforming growth factor receptors in liver regeneration following partial hepatectomy in the rat.
Gruppuso PA, Mead JE, Fausto N. Gruppuso PA, et al. Cancer Res. 1990 Mar 1;50(5):1464-9. Cancer Res. 1990. PMID: 2154324
Cited by
- Hepatobiliary excretion of bacterial formyl-methionyl peptides in rat. Structure activity studies.
Anderson RP, Butt TJ, Chadwick VS. Anderson RP, et al. Dig Dis Sci. 1992 Feb;37(2):248-56. doi: 10.1007/BF01308179. Dig Dis Sci. 1992. PMID: 1735343 - Decreases in TGF-β1 and PDGF levels are associated with echocardiographic changes during adjuvant radiotherapy for breast cancer.
Aula H, Skyttä T, Tuohinen S, Luukkaala T, Hämäläinen M, Virtanen V, Raatikainen P, Moilanen E, Kellokumpu-Lehtinen PL. Aula H, et al. Radiat Oncol. 2018 Oct 19;13(1):201. doi: 10.1186/s13014-018-1150-7. Radiat Oncol. 2018. PMID: 30340644 Free PMC article. - In vitro and in vivo association of transforming growth factor-beta 1 with hepatic fibrosis.
Czaja MJ, Weiner FR, Flanders KC, Giambrone MA, Wind R, Biempica L, Zern MA. Czaja MJ, et al. J Cell Biol. 1989 Jun;108(6):2477-82. doi: 10.1083/jcb.108.6.2477. J Cell Biol. 1989. PMID: 2500447 Free PMC article. - Biomarkers of hepatic fibrosis, fibrogenesis and genetic pre-disposition pending between fiction and reality.
Gressner OA, Weiskirchen R, Gressner AM. Gressner OA, et al. J Cell Mol Med. 2007 Sep-Oct;11(5):1031-51. doi: 10.1111/j.1582-4934.2007.00092.x. J Cell Mol Med. 2007. PMID: 17979881 Free PMC article. Review. - Healing of burn wounds in transgenic mice overexpressing transforming growth factor-beta 1 in the epidermis.
Yang L, Chan T, Demare J, Iwashina T, Ghahary A, Scott PG, Tredget EE. Yang L, et al. Am J Pathol. 2001 Dec;159(6):2147-57. doi: 10.1016/s0002-9440(10)63066-0. Am J Pathol. 2001. PMID: 11733365 Free PMC article.
References
- J Biol Chem. 1972 Dec 10;247(23):7609-11 - PubMed
- J Biol Chem. 1973 May 25;248(10):3528-34 - PubMed
- J Biol Chem. 1979 May 25;254(10):4191-6 - PubMed
- J Clin Invest. 1979 Oct;64(4):948-54 - PubMed
- Cancer Res. 1981 Jul;41(7):2842-8 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources