The potential mechanism for the different expressions of gelatinases induced by all-trans retinoic acid in different cells

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Abstract
Gelatinases include matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The increased expressions of gelatinases are implicated in the pathogenesis of cell injury and cell death. All-trans retinoic acid (ATRA) is an import biological agent which can regulate the expressions of gelatinases and take part in cell injury and cell death. ATRA exerts its biological effect by the high-affinity binding to retinoic acid receptors (RARs). The RARs consist of three isoforms: RAR-α, RAR-β and RAR-γ. However, it is interesting that the effect of ATRA on the expressions of gelatinases is different in different cells. There is no report to explore the possible mechanism for it at present. In this context, we review the published reports and draw a hypothesis that: (i) The distributions of RARs isoforms are different in different cells; (ii) ATRA activates the different RARs isoforms in different cells; (iii) The roles of different RARs isoforms for regulating the expression of MMP-2 or MMP-9 are different in different cells. So, ATRA takes a different function on the expressions of MMP-2 and MMP-9 in different cells. Once the potential strategy can be successfully confirmed, it would be prone to comprehend why the ATRA regulates the different expressions of gelatinases in different cells.

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