Increased expression of transforming growth factor α precursors in acute experimental colitis in rats

Hoffmann, Péter; Zeeh, Jörg M.; Lakshmanan, J.; Wu, Vincent; Procaccino, Frank; Reinshagen, Max; McRoberts, James A.; Ve, Eysselein

doi:10.1136/gut.41.2.195

Cited by 54 publications

(35 citation statements)

References 39 publications

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“…Recently, Hoffman and colleagues have also identified only the precursor forms of TGF-␣ in an acute model of experimental colitis in rats. They propose that the absence of the mature peptide may be due to its rapid removal from the lumen of the inflamed intestine (52). The absence of the mature protein in our ex vivo organ culture supernatants lends further support to their observations that the precursor forms of TGF-␣ may be the true ligands for the EGFR during episodes of inflammation.…”

Section: Discussionsupporting

confidence: 66%

Interactions between stromal cell--derived keratinocyte growth factor and epithelial transforming growth factor in immune-mediated crypt cell hyperplasia.

Bajaj-Elliott¹,

Poulsom²,

Pender³

et al. 1998

J. Clin. Invest.

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Immune reactions in the gut are associated with increased epithelial cell proliferation. Here we have studied the role of keratinocyte growth factor (KGF; FGF7) and transforming growth factor-␣ (TGF-␣ ) in the epithelial cell hyperplasia seen in explants of fetal human small intestine after activation of lamina propria T cells with the superantigen Staphylococcus aureus enterotoxin B (SEB). After the addition of SEB to the explants there is a 10-fold increase in KGF mRNA by 72 h of culture. KGF transcripts were abundant in the lamina propria using in situ hybridization and the culture supernatants contained elevated amounts of KGF protein. SEB had no direct effect on KGF mRNA and protein production by cultured lamina propria mesenchymal cells, but both were upregulated by TNF-␣ . Accompanying the increase in KGF there was also an increase in TGF-␣ precursor proteins in the culture supernatants and the phosphorylated form of the EGFR receptor was also detected in the tissue. Increased TGF-␣ precursor proteins were also detected in the supernatants of control explants stimulated with KGF alone. The direct addition of KGF and TGF-␣ enhanced epithelial cell proliferation and antibodies against KGF and TGF-␣ partially inhibited SEB-induced crypt hyperplasia. These results suggest molecular cross-talk between the KGF/KGFR and the TGF-␣ /EGFR in immunemediated crypt cell hyperplasia. ( J. Clin. Invest. 1998. 102: 1473-1480.)

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Section: Discussionsupporting

confidence: 66%

Interactions between stromal cell--derived keratinocyte growth factor and epithelial transforming growth factor in immune-mediated crypt cell hyperplasia.

Bajaj-Elliott¹,

Poulsom²,

Pender³

et al. 1998

J. Clin. Invest.

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“…The two larger molecular species probably represent precursor peptides of TGF-␣ which were also shown in some previous studies (Hansard et al 1997;Hoffmann et al 1997;Tureaud et al 1997;Wang et al 1997). Using this antibody, no TGF-␣ immunoreactivity was found in colon protein samples from knockout mice ( Figure 3A, Lane 4), but one band of around 25-28 kD was revealed in the sample from wild-type mice ( Figure 3A, Lane 5).…”

Section: Western Immunoblotting For Antibody Specificity Analysismentioning

confidence: 78%

Specificity of the Localization of Transforming Growth Factor-α Immunoreactivity in Colon Mucosa

Chen

Mardell

Read

1999

J Histochem Cytochem.

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SUMMARY Transforming growth factor-␣ (TGF-␣ ) plays an important role in gastrointestinal pathophysiology. However, the exact location of its expression in the intestine is still controversial. This study systematically compared the localization of TGF-␣ immunoreactivity in frozen or fixed human colon using three different antibodies and examined specificity of antibodies by using tissues from TGF-␣ knockout mice and by Western blotting. Consistent with the mRNA distribution revealed by in situ hybridization, a similar staining pattern was obtained in frozen sections by all three antibodies, localizing on the surface and along the crypt epithelium. In paraffin sections, although the polyclonal antibodies (raised against recombinant human or rat TGF-␣ ) gave minimal staining, the monoclonal antibody (against C-terminal peptide of human TGF-␣ ) still gave intense staining on the surface and upper crypt epithelium. By using specimens from TGF-␣ knockout mice in immunostaining and Western blotting, the polyclonal antibodies were shown to be specific. In contrast, specificity of the monoclonal antibody was in doubt in rodent tissues because it gave similar detection between wild-type and knockout mice in both analyses, indicating its crossreaction to non-TGF-␣ molecules. In conclusion, frozen sections and antibodies raised from recombinant TGF-␣ should be used for TGF-␣ immunohistochemistry in the colon. (J Histochem Cytochem 47:949-957, 1999)

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“…However, scarce reports exist about the regulation of TGFA expression in the mucosa [57]. Several studies reported a rapid induction of TGFA expression in models of gut inflammation and mucosal injury [58][59][60][61], suggesting a potential relevance for TGFA in weaning-associated inflammation. Recently, TGFA expression was studied in colon and duodenum during postnatal development in rats [62,63], but to our knowledge this is the first study profiling postnatal TGFA expression in distal small intestine in pigs.…”

Section: Discussionmentioning

confidence: 99%

Intestinal Expression of TFF and Related Genes During Postnatal Development in a Piglet Probiotic Trial

Scholven

Taras²,

Sharbati

et al. 2009

Cell Physiol Biochem

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Trefoil factor family (TFF) peptides provide protective and reparative effects by enhancing epithelial integrity and promoting mucosal restitution. TFF peptide expression is induced after mucosal damage. These processes are of central physiological relevance during the postnatal intestinal development and are strongly influenced during the weaning period. In piglets, weaning at early maturation stages frequently causes mucosal inflammation. The aim of this study was to evaluate postnatal intestinal TFF expression in a piglet probiotic trial. Low intestinal TFF2 expression was measured at early maturation stages. Weaning, however, was associated with a distinct response of increased TFF2 expression, indicating an important role in enhancing mucosal integrity. In the distal jejunum and ileum weaning could as well be associated with increased TFF3 mRNA levels. Differential TFF1 expression was not detected. Furthermore, TFF2 localization studies in different intestinal loci were performed by means of immunohistochemistry. Expression of selected genes (TGFA, EGFR, Cox-2) known to promote TFF signaling showed differential expression pattern as well, thereby providing further functional background. Furthermore, the expression patterns of EGFR observed in this study contribute to an advanced view of previous findings of EGFR regulation mainly obtained in rodents. An upregulated EGFR expression during early postnatal development suggests a local relevance to porcine intestinal maturation. However, a feed supplementation with the probiotic strain Enterococcus faecium did not influence TFF expression.

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Increased expression of transforming growth factor α precursors in acute experimental colitis in rats

Cited by 54 publications

References 39 publications

Interactions between stromal cell--derived keratinocyte growth factor and epithelial transforming growth factor in immune-mediated crypt cell hyperplasia.

Interactions between stromal cell--derived keratinocyte growth factor and epithelial transforming growth factor in immune-mediated crypt cell hyperplasia.

Specificity of the Localization of Transforming Growth Factor-α Immunoreactivity in Colon Mucosa

Intestinal Expression of TFF and Related Genes During Postnatal Development in a Piglet Probiotic Trial

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