蛋白酶和蛋白酶抑制剂(P/PIs)参与人类皮肤的许多生物学过程,然而,通常只调查特定的P/PI家族或相关群体。蛋白质组学方法,比如质谱法,可以定义组织中的蛋白质组特征(包括P/PI);但是,他们努力检测低丰度的蛋白质。为了克服这些问题,我们的目标是产生一个全面的蛋白质组的所有P/PI存在于正常和患病的人类皮肤,在体内,通过使用MEROPS的P/PI列表进行修改的系统审查,并将其与WebofScience中的关键搜索词相结合。根据纳入/排除标准手动审查所得文章,并构建数据集。这项研究确定了人类皮肤中的111种蛋白酶和77种蛋白酶抑制剂,包括丝氨酸,金属-,蛋白酶的半胱氨酸和天冬氨酸催化家族。P/PI没有显示催化活性或蛋白酶抑制的证据,被指定为非肽酶同源物(NPH),和没有报道的蛋白酶抑制活性(NRPIA),分别。MMP9和TIMP1是最常发表的P/PI,在正常皮肤和大多数皮肤疾病组中有报道。正常皮肤和患病皮肤在P/PI方面表现出显著的重叠;然而,MMP23在几个皮肤病组中被发现,但在正常皮肤中不存在。创伤中P/PI的催化谱,疤痕和日光弹性沉着症与正常皮肤不同,表明不同的P/PI组是疾病进展的原因。总之,这项研究使用了一种新的方法来提供我们数据库中报告的正常和患病人类皮肤中P/PI的全面清单。数据库可用于确定哪些P/PI存在于特定疾病中或个体P/PI可能影响哪些疾病。
Proteases and
protease inhibitors (P/PIs) are involved in many biological processes in human skin, yet often only specific families or related groups of P/PIs are investigated. Proteomics approaches, such as mass spectrometry, can define proteome signatures (including P/PIs) in tissues; however, they struggle to detect low-abundance proteins. To overcome these issues, we aimed to produce a comprehensive proteome of all P/PIs present in normal and diseased human skin, in vivo, by carrying out a modified systematic
review using a list of P/PIs from MEROPS and combining this with key search terms in Web of Science. Resulting articles were manually reviewed against inclusion/exclusion criteria and a dataset constructed. This study identified 111 proteases and 77
protease inhibitors in human skin, comprising the serine, metallo-, cysteine and aspartic acid catalytic families of proteases. P/PIs showing no evidence of catalytic activity or
protease inhibition, were designated non-peptidase homologs (NPH), and no reported
protease inhibitory activity (NRPIA), respectively. MMP9 and TIMP1 were the most frequently published P/PIs and were reported in normal skin and most skin disease groups. Normal skin and diseased skin showed significant overlap with respect to P/PI profile; however, MMP23 was identified in several skin disease groups, but was absent in normal skin. The catalytic profile of P/PIs in wounds, scars and solar elastosis was distinct from normal skin, suggesting that a different group of P/PIs is responsible for disease progression. In conclusion, this study uses a novel approach to provide a comprehensive inventory of P/PIs in normal and diseased human skin reported in our database. The database may be used to determine either which P/PIs are present in specific diseases or which diseases individual P/PIs may influence.