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Moreover, accumulating evidence suggests that eicosanoids derived from cyclooxygenase (COX)-2 participate in a number of pathological processes in immune-mediated renal diseases, and it is known that protein kinase B (AKT) may act through different transcription factors in the regulation of the COX-2 promoter. The present results show that progressive accumulation of collagen I in the extracellular medium induces a significant increase of COX-2 expression in human mesangial cells, resulting in an enhancement in PGE<jats:sub>2<\/jats:sub> production. COX-2 overexpression is due to increased COX-2 mRNA levels. The study of the mechanism implicated in COX-2 upregulation by collagen I showed focal adhesion kinase (FAK) activation. Furthermore, we observed that the activation of the phosphatidylinositol 3-kinase (PI3K)\/AKT pathway by collagen I and collagen I-induced COX-2 overexpression was abolished by PI3K and AKT inhibitors. Additionally, we showed that the cAMP response element (CRE) transcription factor is implicated. Finally, we studied COX-2 expression in an animal model, N<jats:sup>G<\/jats:sup>-nitro-l-arginine methyl ester hypertensive rats. In renal tissue and vascular walls, COX-2 and collagen type I content were upregulated. In summary, our results provide evidence that collagen type I increases COX-2 expression via the FAK\/PI3K\/AKT\/cAMP response element binding protein signaling pathway. <\/jats:p>","DOI":"10.1152\/ajpcell.00176.2010","type":"journal-article","created":{"date-parts":[[2011,1,6]],"date-time":"2011-01-06T03:57:10Z","timestamp":1294286230000},"page":"C907-C918","source":"Crossref","is-referenced-by-count":8,"title":["Changes in extracellular matrix composition regulate cyclooxygenase-2 expression in human mesangial cells"],"prefix":"10.1152","volume":"300","author":[{"given":"Matilde","family":"Alique","sequence":"first","affiliation":[{"name":"Departamento de Fisiolog\u00eda,"},{"name":"Inststuto Reina Sof\u00eda de Investigaci\u00f3n Nefrol\u00f3gica, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Calleros","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda,"},{"name":"Inststuto Reina Sof\u00eda de Investigaci\u00f3n 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