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Human transforming growth factor (TGF-) is digested to a smaller (1–43), less biologically active, form in acidic gastric juice

¹ Imperial College Faculty of Medicine, Department of Gastroenterology, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
² Department of Gastroenterology, Middlesex Hospital, Sterling Way, Edmonton, London N18 1QX, UK
³ Imperial Cancer Research Fund, Lincolns Inn Fields, London W2C 2PX, UK

Correspondence to:
Correspondence to:
Professor R J Playford, Gastroenterology Section, Imperial College School of Medicine, Hammersmith Hospital Campus, Du Cane Rd, London W12 0NN, UK;
r.playford{at}ic.ac.uk

ABSTRACT
Background: Transforming growth factor (TGF-) is a 50 amino acid peptide with potent proliferative and cytoprotective activity present in gastric mucosa and juice.

Aims: To determine the forms and biological activity of natural and recombinant TGF- following incubation with acid pepsin.

Patients: Human gastric juice was obtained under basal conditions from patients taking acid suppressants and from volunteers undergoing intragastric neutralisation.

Methods: Samples were analysed using mass spectroscopy and/or high pressure liquid chromatography with radioimmunoassay. Biological activity was determined using thymidine incorporation into rat hepatocytes and an indomethacin/restraint induced gastric damage rat model.

Results: TGF-_1–50 is cleaved to TGF-_1–43 by acid pepsin and this is the predominant form in normal gastric juice. However, intragastric neutralisation or taking acid suppressants caused the predominant form to be TGF-_1–50. TGF-_1–43 had only half of the ability to maximally stimulate [³H]thymidine incorporation into primary rat hepatocytes (28 177 (1130) DPM/well for 2.16 nM TGF-_1–43 v 63 184 (3536) DPM/well for TGF-_1–50; p<0.001). A similar reduced potency was seen when used in an indomethacin induced rat gastric damage model (0.18 µmol/kg/h of TGF-_1–43 reduced ulcer area by 19% whereas TGF-_1–50 reduced area by 62%; p<0.001).

Conclusions: TGF-_1–50 is cleaved to the TGF-_1–43 form by acid pepsin, causing 2–5-fold loss of biological activity. Such changes may have relevance to the actions of acid suppressants and the importance of this peptide in both normal and abnormal growth.

Keywords: transforming growth factor; gastric juice

Abbreviations: HPLC, high pressure liquid chromatography; AcN, acetonitrile; TFA, trifluoroacetic acid; EGF, epidermal growth factor; EGF-R, epidermal growth factor receptor; PPI, proton pump inhibitor; RIA, radioimmunoassay; TGF-, transforming growth factor

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