Effects of Male Circumcision on Human Penile Epithelia

描述（由申请人提供）：男性包皮环切术已被证明在降低非洲男性艾滋病毒感染率方面具有临床效果。减少艾滋病毒传播的科学原理仍然未知，我们实验室的工作表明，这种机制比早期理论（关于角蛋白厚度和潜在的艾滋病毒靶细胞数量）复杂得多。我们发现阴茎上皮细胞的更多动态特性，如渗透性和炎症反应，可能起着更重要的作用。本研究旨在进一步探讨男性包皮环切术后阴茎上皮细胞的变化，这些变化与皮肤的屏障功能有关，并将其与以前接受过包皮环切术和未接受包皮环切术的人群进行比较。辅助研究将侧重于包皮中基线连接蛋白表达和可能影响男性HIV感染的临床因素的研究。通过这些研究，我们希望更好地了解艾滋病毒如何在男性生殖道中通过性传播，男性包皮环切术如何预防这种情况，以及如何制定有效的艾滋病毒预防未来战略。

DESCRIPTION (provided by applicant): Male circumcision has been shown to be clinically effective in reducing HIV acquisition rates in African men. The scientific rationale for the reduction in HIV transmission remains unknown, and work in our laboratory has shown that the mechanism is much more complex than those theorized early on (regarding keratin thicknesses and number of potential HIV target cells). We have found that more dynamic properties of the penile epithelia, such as permeability and inflammatory responses, may play more important roles. This proposal endeavors to further explore changes in penile epithelia after male circumcision, which relate to the skin's barrier function, and to compare them to previously circumcised and uncircumcised cohorts. Adjunct studies will focus on studies of baseline junctional protein expression in the foreskin and clinical factors that may affect HIV susceptibiliy in men. With these studies, we hope to gain a better understanding of how HIV is sexually transmitted in the male genital tract, how male circumcision works to prevent this, and how to develop effective future strategies in HIV prevention.