Cellular and Molecular Mechanisms of Gastrointestinal Ulcer Healing

Tarnawski, Andrzej S.

doi:10.1007/s10620-005-2803-6

Cited by 354 publications

(312 citation statements)

References 45 publications

(117 reference statements)

Supporting

Mentioning

276

Contrasting

Unclassified

Order By: Relevance

Section: Discussionmentioning

confidence: 99%

“…33 It has been known for many years that prostaglandins are important mediators of many of the processes involved in ulcer healing. 33,34 Moreover, prostaglandins derived from COX-2 appear to be particularly important in ulcer healing. 26,34 COX-2 is important both in re-epithelialization and angiogenesis, and has been shown to be expressed primarily at the ulcer margin.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Muc-2–Deficient Mice Display a Sex-Specific, COX-2–Related Impairment of Gastric Mucosal Repair

Wallace

Vong

Dharmani

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Mucus is known to contribute significantly to the prevention and repair of mucosal damage throughout the gastrointestinal tract. Although not normally expressed in the stomach, mucin-2 (MUC-2, encoded by the MUC2 gene) is expressed in certain disease states. The aim of this study was to determine in a mouse model whether the absence of Muc-2 would result in impaired susceptibility to and healing of gastric mucosal injury. Acute gastric damage was induced in mice deficient in Muc-2 and in wild-type controls, through oral administration of indomethacin. Chronic gastric ulcers were induced by serosal application of acetic acid. The extent of injury and the extent of healing of the damage over time were examined in both models. Indomethacin administration caused similar levels of gastric damage in Muc-2-deficient and wild-type mice, but the erosions healed more slowly in the former. Acetic acid-induced gastric ulcers were initially similar in size in Muc-2-deficient and wildtype mice of both sexes, but ulcer healing was significantly impaired in male Muc-2-deficient mice. Induction of cyclooxygenase-2 in the stomach, in response to indomethacin-or acetic acid-induced ulceration, was significantly reduced in male Muc-2-deficient mice. This phenomenon, and the sex specificity, was also apparent in bone marrow-derived macrophages stimulated with endotoxin. These results demonstrate a marked impairment of gastric mucosal repair in male Muc-2-deficient mice that may be related to an insufficient induction of cyclooxygenase-2, an enzyme known to contribute to mucosal repair.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Muc-2–Deficient Mice Display a Sex-Specific, COX-2–Related Impairment of Gastric Mucosal Repair

Wallace

Vong

Dharmani

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…For example, although it was reported that vascular endothelial growth factor (VEGF) played a role in ulcer healing process [6], it is known as an important factor in tumor angiogenesis [7]. Therefore, target-selective or -specific gene transfer is desirable for maximal therapeutic action and minimal adverse effects in the clinical use of gene therapy.…”

Section: Introductionmentioning

confidence: 99%

Improved stomach selectivity of gene expression following microinstillation of plasmid DNA onto the gastric serosal surface in mice

Nishi

Fumoto

Ishii

et al. 2008

European Journal of Pharmaceutics and Biopharmaceutics

View full text Add to dashboard Cite

Stomach-selective gene transfer is a promising approach as a therapeutic strategy for refractory gastric diseases. In this study, we improved the stomach selectivity of gene expression following microinstillation of naked plasmid DNA (pDNA) onto the gastric serosal surface in mice. pDNA encoding firefly luciferase was used as a reporter gene. It was confirmed that the gene expression level in the stomach 6 h after gastric serosal surface microinstillation of pDNA was significantly higher than after intragastric, intraperitoneal and intravenous administration. Regarding selectivity of gene expression, the gene expression level in the stomach after gastric serosal surface microinstillation of 1 µg/1 µL (dose/volume) pDNA was 5.7 times higher than that in the spleen. In our previous study (30 µg/30 µL), the expression level in the stomach was 2.7 times higher than that in the spleen; therefore, the selectivity was 2.1 times higher in this study. When we investigated gene expression at various pDNA solution concentrations, the ratio of the gene expression level in the stomach to that in the spleen was the highest as 1 µg/1 µL of pDNA, which was considered the optimal concentration. Information in this study is useful for further development of target organ-selective gene delivery systems.

show abstract

“…Mitogenic signals associated with ERK1/2 MAP kinase and early growth response gene 1 (EGR-1) during gastrointestinal injury mediated the epithelium recovery processes after NSAID exposure. Epithelial toxic stresses have been known to stimulate the compensatory signals of wound healing and tissue reconstitution including growth factor-activated rasassociated MAP kinase pathway and other small GTP-binding protein family signals as well (Guo et al, 2003;Tarnawski, 2005). Rho small GTPases such as RhoA, CDC42, and Rac1 GTPas are a multimember family of RAS small GTPase, which are also mitogenic and tumorigeneic when overexpressed in the intestinal epithelium.…”

Section: Introductionmentioning

confidence: 99%

Growth compensatory role of sulindac sulfide-induced thrombospondin-1 linked with ERK1/2 and RhoA GTPase signaling pathways

et al. 2008

View full text Add to dashboard Cite

Previously, we reported that non-steroidal anti-inflammatory drugs (NSAIDs) suppress cellular invasion which was mediated by thrombospondin-1 (TSP-1). As the extending study of the previous observation, we investigated the effect of NSAID-induced TSP-1 on the cellular growth and its related signaling transduction of the TSP-1 production. Among diverse NSAIDs, sulindac sulfide was most potent of inducing the human TSP-1 protein expression. Functionally, induced TSP-1 expression was associated with the growth-compensatory action of NSAID. TSP-1 expression was also elevated by mitogenic signals of ERK1/2 and RhoA GTPase pathway which had also growthpromotive capability after sulindac sulfide treatment. These findings suggest the possible mechanism through which tumor cells can survive the chemopreventive action of NSAIDs or the normal epithelium can reconstitute after NSAID-mediated ulceration in a compensatory way.

show abstract

Cellular and Molecular Mechanisms of Gastrointestinal Ulcer Healing

Cited by 354 publications

References 45 publications

Muc-2–Deficient Mice Display a Sex-Specific, COX-2–Related Impairment of Gastric Mucosal Repair

Muc-2–Deficient Mice Display a Sex-Specific, COX-2–Related Impairment of Gastric Mucosal Repair

Improved stomach selectivity of gene expression following microinstillation of plasmid DNA onto the gastric serosal surface in mice

Growth compensatory role of sulindac sulfide-induced thrombospondin-1 linked with ERK1/2 and RhoA GTPase signaling pathways

Contact Info

Product

Resources

About