Distribution of heparan sulfate correlated with the expression of heparanase-1 and matrix metalloproteinase-9 in an ovariectomized rats skin.

There are few studies on heparan sulfate (HS) in the skin, during aging, when estrogen is suppressed. The enzyme heparanase-1 (HPSE-1), has its 17β-estrogen-regulated expression in pathological conditions such as cancer and chronic inflammatory diseases. HPSE-1 is correlated with the matrix metalloproteinase-9 (MMP-9), an endopeptidase that also undergoes estrogen action. We investigated the distribution of HS, expression HPSE-1 and MMP-9 in the skin of adult rats at different ages and in the age-matched ovariectomized rats to evaluate the influence of low estrogen on the distribution of HS. Thirty female Wistar rats were used. Rats underwent to a sham surgery (ctr, n = 15) or to a bilateral ovariectomy (ovx, n = 15) and were euthanized after 45, 75, and 90 days after ovariectomy. Morphological, morphometric, biochemical, and reverse transcriptase polymerase chain reaction (RT-PCR) methodologies were used. A significant decrease (P < 0.001) in total skin thickness was observed in the ctr and ovx animals, being higher in the older animals. The thickness of the epidermis and dermis decreased; however, the proportion in the total skin remained similar comparing ctr and ovx. An increase of HS with increasing age and ovariectomy was observed. The expression of the HPSE-1 and MMP-9 enzymes decreased, being higher in old animals. A correlation between the increase of HS and the decrease of the HPSE-1 was demonstrated in both groups. Overall, these data suggested that estrogen acts in the regulation of the expression of the HPSE-1, not only in pathological states, as already established, but also in aging.

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