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

Abstract

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.