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Expression of Urokinase-Type Plasminogen Activator and Its Receptor in Gastric Fibroblasts and Effects of Nonsteroidal Antiinflammatory Drugs and Prostaglandin

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An Erratum to this article was published on 08 December 2011

Abstract

In acute inflammatory condition, little is known about the expression of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in the gastric fibroblasts. To clarify the role of human gastric fibroblasts in acute inflammatory conditions such as gastric ulcer, the effects of interleukin (IL)-1β and tumor necrosis factor (TNF)-α on the expression of uPA and uPAR, which were suggested to be associated with tissue remodeling, in gastric fibroblasts were investigated. The expression level of uPA mRNA and the amount of uPA antigen increased significantly on treatment with each concentration of IL-1β (1 and 10 ng/ml) and 10 ng/ml TNF-α. On the other hand, the amounts of uPA antigen on cell surfaces were not affected significantly by IL-1β and TNF-α stimulation. The expression level of uPAR mRNA increased in a dose-dependent manner on IL-1β stimulation. The effect of indomethacin on uPA and uPAR expression in these cells was also examined. When gastric fibroblasts were treated with 50 μM indomethacin, the expression level of uPA mRNA decreased significantly, and the amount of uPA antigen in the culture medium and on cell surfaces decreased significantly with indomethacin in a dose-dependent manner. The increased uPAR mRNA expression caused by IL-1β was reduced to the basal level by treatment with 50 μM indomethacin. Furthermore, we investigated the role of prostaglandin E2 (PGE2), which is suggested to play major roles in acute inflammation of the stomatch, on uPA and uPAR expression in gastric fibroblasts. The expression level of uPAR mRNA and the amount of uPA antigen on cell surfaces increased in a dose-dependent manner on treatment with PGE2 (10 and 50 ng/ml). These results suggest that uPA and uPAR expression in gastric fibroblasts is involved in the regulating system of PGE2 and that NSAIDs may delay healing of gastric mucosal injury in part through suppressing uPA production via inhibition of endogenous PG production.

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Authors and Affiliations

  1. The Fifth Department of Internal Medicine, Tokyo Medical University, Ibaraki, Japan

    Jun-Ichi Iwamoto, Kimiko Takahashi, Yuji Mizokami, Toshiya Otsubo, Syuuhei Miura, Toshiaki Narasaka, Hiroki Takeyama, Takayuki Omata, Kouichi Shimokoube & Takeshi Matsuoka

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  1. Jun-Ichi Iwamoto
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  2. Kimiko Takahashi
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Correspondence to Jun-Ichi Iwamoto.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s10620-011-2005-3

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Iwamoto, JI., Takahashi, K., Mizokami, Y. et al. Expression of Urokinase-Type Plasminogen Activator and Its Receptor in Gastric Fibroblasts and Effects of Nonsteroidal Antiinflammatory Drugs and Prostaglandin. Dig Dis Sci 48, 2247–2256 (2003). https://doi.org/10.1023/B:DDAS.0000007859.10680.b1

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