Localization and regulation of pregnancy-associated plasma protein a expression in healing human skin
Localization and regulation of pregnancy-associated plasma protein a expression in healing human skin
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DOI：
10.1210/jc.2003-030193
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发表时间：
2003-09-01
影响因子：
5.8
通讯作者：
Conover, CA
中科院分区：
文献类型：
--
作者：
Chen, BK;Leiferman, KM;Conover, CA
妊娠相关血浆蛋白A（PAPP-A）是一种IGF结合蛋白-4（IGFBP-4）金属蛋白酶，其在体外切割抑制性IGFBP-4以放大局部IGF-I生物利用度。因此，它在损伤/修复反应中具有功能意义。在这项研究中，我们确定了PAPP-A在愈合的人类皮肤中的表达。用手术刀在三名正常受试者的前臂上诱导伤口，并允许其通过第一意图愈合。对第0、2、8和14天获得的活检组织进行PAPP-A、IGF-I和IGFBP-4的免疫组织化学检测。在未受伤的皮肤（D 0），强烈的染色PAPP-A存在于表皮，汗液和皮脂腺上皮细胞，毛囊，血管;没有PAPP-A检测到真皮成纤维细胞或成熟的胶原束。IGF-I主要分布于皮肤腺体的上皮细胞，在表皮和血管中分布较弱，在真皮细胞中不表达。在未损伤的表皮中发现IGFBP-4的弱灶性染色。在伤口愈合过程中，PAPP-A的表达诱导真皮肉芽组织内和附近的伤害。PAPP-A在第2天出现在真皮中，在第8天和第14天的强度和范围增加。表皮中PAPP-A表达也增加。PAPP-A在肉芽组织细胞中的表达与肌成纤维细胞和新血管的α-平滑肌动蛋白染色以及巨噬细胞的CD 68染色共定位，并且与愈合伤口的致密的新合成的胶原蛋白相关。IGF-I染色在切口区域的表皮和与淋巴样细胞相关的肉芽组织中增强。表皮的IGFBP-4染色在伤口愈合期间保持不变，但随着时间的推移在肉芽组织的成纤维细胞中被诱导。这些数据表明PAPP-A在人皮肤中的定位和调节表达，并表明PAPP-A可能在体内伤口愈合和组织重塑中的整合IGF系统中发挥重要作用。
Pregnancy-associated plasma protein A (PAPP-A) is an IGF-binding protein-4 (IGFBP-4) metalloproteinase that cleaves inhibitory IGFBP-4 to amplify local IGF-I bioavailability in vitro. Thus it has functional implications in injury/repair responses. In this study we determined PAPP-A expression in healing human skin. Wounds were induced with a scalpel on the forearms of three normal subjects and were allowed to heal by first intention. Biopsies obtained on d 0, 2, 8, and 14 were processed for immunohistochemical detection of PAPP-A, IGF-I, and IGFBP-4. In uninjured skin (d 0), strong staining for PAPP-A was present in the epidermis, sweat and sebaceous gland epithelial cells, hair follicles, and blood vessels; no PAPP-A was detected in dermal fibroblasts or with mature collagen bundles. IGF-I localized strongly to epithelial cells of skin glands was weak to moderate in epidermis and blood vessels, and was absent in dermal cells. Weak focal staining for IGFBP-4 was found within uninjured epidermis. During wound healing, PAPP-A expression was induced in dermal granulation tissue within and adjacent to the injury. PAPP-A was present in dermis on d 2 and was increased in intensity and extent on d 8 and 14. PAPP-A expression also increased in the epidermis. PAPP-A expression in cells of granulation tissue colocalized with alpha-smooth actin staining of myofibroblasts and new blood vessels as well as with CD68 staining of macrophages and was associated with the compact, newly synthesized collagen of the healing wound. IGF-I staining was enhanced in the epidermis localized to the area of the incision and in granulation tissue associated with lymphoid cells. IGFBP-4 staining of the epidermis remained unchanged during wound healing, but was induced in the fibroblastic cells of granulation tissue over time. These data demonstrate localized and regulated expression of PAPP-A in human skin and suggest that PAPP-A may play an important role in an integrated IGF system in wound healing and tissue remodeling in vivo.