PRSS3 was also limited to the epithelium but mRNA levels were not increased in vaginal tissues from women with prolapse. Limitations in the amount of tissue available precluded a comprehensive GW-610742 analysis of 25 kDa enzyme activity in the human. Nonetheless, SERPINA1 was MCE Company Duvoglustat decreased in stromal tissues from pre- and postmenopausal women with prolapse and in epithelium from menopausal women with POP. Elafin was also decreased significantly in tissues from women with prolapse. The role of a1-antitrypsin has been well studied in pulmonary emphysema, in which reduction of a1-antitrypin leads to destruction of elastin ECM, resulting in enlargement of alveoli. Conversely, overexpression of a1-antitrypsin in cigarette smokeinduced and VEGF-inhibition-induced, proteolysis-independent pulmonary emphysema models suggested that a1-antitrypsin serves not only as an inhibitor of elastase but also possesses elastase-independent anti-apoptosis functions in vivo. It has been suggested that apoptotic cells are increased in pelvic tissues from women with prolapse, and a1-antitrypsin mRNA was reported to be decreased in postmenopausal women with POP relative to postmenopausal women without POP. Another report, however, did not find any positive correlation between the site of a1-antitrypsin expression and posterior/anterior ratio in bladder and uterine prolapse. Therefore, our report has shown for the first time that a1-antitrypsin levels were decreased in menopausal women with POP compared to control. It is interesting to note that in some cases, protease regulation by inhibitors differed in humans and Fbln52/2 mice with prolapse. For example, the serine protease inhibitor, Elafin, which is regulated primarily by its transcript level, was decreased in epithelium from women with prolapse. In contrast, we observed marked upregulation of Elafin transcripts in epithelium of Fbln52/2 vagina. In the complete absence of fibulin-5, Elafin may not localize to the matrix and its mRNA may be upregulated dramatically as a compensatory manner. In women with prolapse, however, in which fibulin-5 may be compromised but not absent, Elafin may play a more substantial role in inhibiting elastase-mediated matrix degradation. Although SERPINB7 was not investigated with adequate power, our pilot st
