The role of extracellular matrix in injury to gastric mucosa by indomethacin.

The extracellular matrix components fibronectin, collagen IV, and laminin provide structural support for the gastric mucosal cells and influence cell migration, attachment, differentiation, and proliferation. Because little is known about the effect of indomethacin on the extracellular matrix, we studied the expression and distribution of extracellular matrix components in the gastric mucosa before and sequentially during indomethacin injury. A total of 32 male Sprague-Dawley rats were treated with placebo or indomethacin 100 mg intraperitoneally. One, 4, and 18 h later, stomachs were excised and gastric specimens were immunostained with specific antibodies against fibronectin (FN), collagen IV (CIV), laminin (LM), fibronectin receptor (FNR), and vimentin (VM). Gross necrosis, quantitative histology, and expression of FN, CIV, LM, FNR, and VM were analyzed using a videoimage analysis system. In the mucosa treated with indomethacin, the expression of VM and LM was decreased by 54% (p < 0.01) and 52% (p < 0.01), respectively, within 1 h vs. control mucosa. The former reflected damage to endothelial cells. Expression of FN, FNR, and CIV was decreased by 50, 25, and 50%, respectively, at 1 h after indomethacin, reflecting significant damage to the extracellular matrix. However, at 1 h, no gross necrosis and no histologic damage were seen in the gastric mucosa. We conclude that expression of extracellular matrix components in the gastric mucosa is significantly reduced during indomethacin injury and that damage to extracellular matrix and microvascular endothelium precedes injury of glandular epithelial cells.