Reduction of EGF is associated with the delay of ulcer healing by cigarette smoking

Ma, Li; Wang, W. P.; Chow, Jennifer; Yuen, Siu Tsan; Cho, C. H.

doi:10.1152/ajpgi.2000.278.1.g10

Cited by 46 publications

(45 citation statements)

References 34 publications

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“…3B). To investigate whether rCRAMP influenced proliferation and angiogenesis by induction of EGF and/or vascular endothelial growth factor synthesis (Jones et al, 1999;Ma et al, 2000), we determined the protein levels of these factors in the gastric mucosa on day 4 after ulcer induction and found that their expression was not affected by the rCRAMP gene therapy (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…Gastric kissing ulcers were produced by luminal application of acetic acid. Animals were sacrificed on days 1, 4, 7, and 10 after ulcer induction, and the ulcer area was measured as described previously (Ma et al, 2000) by a person who was unaware of the type of treatment. After measuring the ulcerated area, a longitudinal section of stomach along the greater curvature, including the ulcer base and both sides of the ulcer margin, was fixed in 4% buffered formalin for 24 h at 4°C for histologic study.…”

Section: Methodsmentioning

confidence: 99%

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The Cationic Host Defense Peptide rCRAMP Promotes Gastric Ulcer Healing in Rats

Yang

Wu²,

Tai³

et al. 2006

J Pharmacol Exp Ther

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Cathelicidin, a cationic host defense peptide, has been shown to promote cutaneous wound repair and reaches high levels in the gastric mucosa during infection and inflammation. Therefore, we investigated whether this peptide contributes to gastric ulcer healing in rats. Ulcer induction increased the expression of rat cathelicidin rCRAMP in the gastric mucosa. Further increase in expression of rCRAMP by local injection of rCRAMPencoding plasmid promoted ulcer healing by enhancing cell proliferation and angiogenesis. rCRAMP directly stimulated proliferation of cultured rat gastric epithelial cells (RGM-1), which was abolished by inhibitors of matrix metalloproteinase (MMP), epidermal growth factor receptors (EGFR) tyrosine kinase, or mitogen-activated protein kinase/extracellular signalregulated kinase (ERK) kinase. rCRAMP also increased EGFR and ERK1/2 phosphorylation via an MMP-dependent mechanism. Knockdown of transforming growth factor ␣ (TGF␣), which is a ligand of EGFR, by small interfering RNA completely nullified the mitogenic signals evoked by rCRAMP in RGM-1 cells. These findings suggest that rCRAMP exhibits prohealing activity in stomachs through TGF␣-dependent transactivation of EGFR and its related signaling pathway to induce proliferation of gastric epithelial cells.The gastrointestinal tract is constantly exposed to a repertoire of potentially detrimental agents that may inflict tissue injury. On such injury, a repair process is initiated that comprises migration, proliferation, and differentiation of parenchymal and mesenchymal cells in the gastrointestinal mucosa (Podolsky, 1999). Many endogenous molecules that regulate these cellular responses have been identified Taupin and Podolsky, 2003). Little studied in this panoply of factors are the host defense peptides, which were originally characterized as small cationic peptides that could kill microbes. This group of peptides is now recognized to contain multifunctional molecules that can modulate many host cellular responses (Li et al., 2000;Selsted and Ouellette, 2005).Cathelicidins constitute a class of host defense peptides in mammals (Zaiou and Gallo, 2002). They are synthesized as preproprotein, which is characterized by an N-terminal signal sequence, a well conserved cathelin-like domain, and a C-terminal peptide domain that is proteolytically cleaved to release a small molecular weight host defense peptide. The mature peptides vary markedly among different species. Many mammals such as pigs and cattle have multiple cathelicidin genes, whereas humans, mice, and rats have only one, designated as LL-37/hCAP-18, mCRAMP, and rCRAMP, respectively. The peptide is present in phagocytic granulocytes, the first type of cell to be recruited from the blood to sites of infection and injury, and on surfaces in contact with the outside environment like skin epithelium (Termen et al., 2003). In the gastrointestinal tract, LL-37, the mature peptide of human cathelicidin, is produced constitutively by differentiated surface and upper crypt epithelial ...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The Cationic Host Defense Peptide rCRAMP Promotes Gastric Ulcer Healing in Rats

Yang

Wu²,

Tai³

et al. 2006

J Pharmacol Exp Ther

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“…Smoking has also been shown to reduce levels of various growth factors (31). It is thus likely that both cigarette smoking and chronic hypoxia decreased mucosal integrity and, as a result, mucosal injury was readily induced at lower dosages of prednisolone in CSE rats.…”

Section: Discussionmentioning

confidence: 99%

Vulnerability of Gastric Mucosa to Prednisolone in Rats Chronically Exposed to Cigarette Smoke

Takeuchi

Takahashi²,

Fuchikami³

2008

J Pharmacol Sci

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Abstract. We examined gastric mucosal vulnerability in a rat model of chronic obstructive pulmonary disease (COPD). Male Wistar rats were exposed to cigarette smoke for 12 weeks (CSE rats), and on the last 4 days of exposure, prednisolone was given to induce gastric mucosal injury. Histopathology, pulmonary function, arterial blood gases, and levels of lipid peroxides (LPO), prostaglandin E 2 (PGE 2 ), hypoxia-inducible factor 1 alpha subunit (HIF-1α), and vascular endothelial growth factor (VEGF) in gastric mucosa were examined. We also tested the effect of rebamipide on prednisolone-induced gastric lesions. In CSE rats, although no gastric lesions were detected, LPO, PGE 2 , HIF-1α, and VEGF levels were higher than in control rats. Prednisolone induced gastric hemorrhagic lesions more readily in CSE rats than controls, with concomitant decrease in PaO 2 and increased levels of LPO, HIF-1α, and VEGF. Rebamipide reversed gastric lesions without affecting any parameters examined. CSE rats were found to be a useful animal model of COPD, and COPD appeared to render the gastric mucosa vulnerable to prednisolone.

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“…The detrimental effect of smoking is exhibited by inhibition of cell proliferation, mucus secretion and angiogenesis due to deficiency in EGF biosynthesis and its mRNA expression. The shortage of these factors is responsible for the delay in ulcer healing (104). Several spices and plant extracts such as Mexican tea herb and pilular adina herb, Chuanxiong spices, Capsaicin, Kuiyangping, Weitongning and Angelica sinensis interact with EGF synthesis and hence contribute to the gastroprotection.…”

Section: Herbs and Egfmentioning

confidence: 99%

Spices as Alternative Agents for Gastric Ulcer Prevention and Treatment

Mofleh¹

2011

Peptic Ulcer Disease

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Reduction of EGF is associated with the delay of ulcer healing by cigarette smoking

Cited by 46 publications

References 34 publications

The Cationic Host Defense Peptide rCRAMP Promotes Gastric Ulcer Healing in Rats

The Cationic Host Defense Peptide rCRAMP Promotes Gastric Ulcer Healing in Rats

Vulnerability of Gastric Mucosa to Prednisolone in Rats Chronically Exposed to Cigarette Smoke

Spices as Alternative Agents for Gastric Ulcer Prevention and Treatment

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