Department of Morphology and Physiology, Faculdade de Medicina ABC, Av. Lauro Gomes, 2000 - Vila Sacadura Cabral, Santo André, São Paulo, 09060-870, Brazil.
Vivarium, Faculdade de Medicina ABC, Av. Lauro Gomes, 2000 - Vila Sacadura Cabral, Santo André, São Paulo, 09060-870, Brazil.
Cell Biol Int. 2020 Jul;44(7):1458-1466. doi: 10.1002/cbin.11339. Epub 2020 Mar 27.
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.
关于在衰老过程中、雌激素被抑制时皮肤中的硫酸乙酰肝素（HS）的研究较少。在癌症和慢性炎症性疾病等病理条件下，酶类 17β-雌激素调节表达的肝素酶-1（HPSE-1）与其基质金属蛋白酶-9（MMP-9）相关，后者也是一种受雌激素作用影响的内肽酶。我们研究了 HS 在不同年龄的成年大鼠皮肤中的分布，以及在年龄匹配的卵巢切除大鼠中的表达，以评估低雌激素对 HS 分布的影响。使用了 30 只雌性 Wistar 大鼠。大鼠接受假手术（ctr，n = 15）或双侧卵巢切除术（ovx，n = 15），并在卵巢切除后 45、75 和 90 天处死。使用了形态学、形态计量学、生化和逆转录聚合酶链反应（RT-PCR）方法。在 ctr 和 ovx 动物中，总皮肤厚度显著降低（P < 0.001），老年动物的降低更为明显。表皮和真皮的厚度均减少；然而，ctr 和 ovx 之间的总皮肤比例相似。随着年龄的增长和卵巢切除，HS 表达增加。HPSE-1 和 MMP-9 酶的表达减少，老年动物的表达更高。在两组中均证明了 HS 的增加与 HPSE-1 的减少之间存在相关性。总的来说，这些数据表明，雌激素不仅在已确定的病理状态下，而且在衰老过程中也会调节 HPSE-1 的表达。
