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Updated: May 11, 2026

In vivo Liver Endocytosis Followed by Purification of Liver Cells by Liver Perfusion
12:35

In vivo Liver Endocytosis Followed by Purification of Liver Cells by Liver Perfusion

Published on: November 10, 2011

Hepatic processing of transforming growth factor beta in the rat. Uptake, metabolism, and biliary excretion

R J Coffey, L J Kost, R M Lyons

    The Journal of Clinical Investigation
    |September 1, 1987
    PubMed

    Insights

    The liver rapidly extracts and processes transforming growth factor beta (TGF beta), excreting its metabolites through bile. This hepatic metabolism involves lysosomes and microtubules, identifying the liver as a key site for TGF beta disposition.

    Area of Science:

    • Cell biology
    • Pharmacology
    • Hepatology

    Background:

    • Transforming growth factor beta (TGF beta) is a polypeptide that regulates cell growth.
    • Its in vivo disposition and metabolic fate remain largely unknown.
    • Understanding TGF beta's processing is crucial for its therapeutic applications.

    Purpose of the Study:

    • To investigate the hepatic processing and in vivo disposition of biologically active 125I-TGF beta in rats.
    • To identify the cellular mechanisms and organelles involved in TGF beta metabolism.
    • To explore the role of the liver in TGF beta clearance and excretion.

    Main Methods:

    • Intravenous and intrafemoral administration of 125I-TGF beta in rats.
    • Partial hepatectomy to assess the liver's role in clearance.
    • Isolated perfused rat liver model to study hepatic extraction.
    • Pharmacological inhibition (colchicine, vinblastine, chloroquine, leupeptin) and fasting.
    • Liver fractionation and molecular sieve chromatography.

    Main Results:

    • 125I-TGF beta exhibited rapid plasma disappearance (t1/2 = 2.2 min), significantly delayed by partial hepatectomy.
    • The liver was the primary organ for extraction (63% in liver/bile within 90 min).
    • Hepatic extraction (36%) was inhibited by unlabeled TGF beta and lectins, and reduced by fasting.
    • Metabolites were excreted into bile, with lysosomal and microtubule involvement suggested by fractionation and drug studies.

    Conclusions:

    • The liver efficiently and selectively extracts biologically active TGF beta from circulation.
    • TGF beta undergoes transhepatic transport, intracellular metabolism (lysosome-associated), and biliary excretion of metabolites.
    • The liver is a major site for TGF beta metabolism and disposition.

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