A mechanistic evaluation of human beta defensin 2 mediated protection of human skin barrier in vitro.
A mechanistic evaluation of human beta defensin 2 mediated protection of human skin barrier in vitro.
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DOI：
10.1038/s41598-023-29558-0
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发表时间：
2023-02-08
影响因子：
4.6
通讯作者：
Davidson, Donald J.
中科院分区：
文献类型：
--
作者：
Shelley, Jennifer R.;McHugh, Brian J.;Wills, Jimi;Dorin, Julia R.;Weller, Richard;Clarke, David J.;Davidson, Donald J.
人类皮肤屏障是一种生物必需品，在炎症性皮肤病如特应性皮炎（AD）中受损。金黄色葡萄球菌与AD病变相关，并导致病理性炎症和进一步的屏障损伤。S.金黄色葡萄球菌分泌细胞外蛋白酶，如V8（或“SspA”），其切割细胞外蛋白以减少皮肤屏障。先前的研究表明，宿主防御肽人β-防御素2（HBD 2）可预防V8介导的损伤。在这里，HBD 2介导的屏障保护在体外的机制进行了检查。外源性HBD 2的应用提供了针对V8的保护，无论应用的时间轴或天然肽折叠如何，提高了简单肽类似物作为治疗剂的前景。在V8介导的损伤的背景下，HBD 2治疗调节HaCaT细胞的蛋白质组/分泌组谱，改变特异性细胞外基质蛋白的水平，潜在地恢复V8损伤。然而，在没有损伤的情况下，单独的HBD 2基本上不调节细胞蛋白质组/分泌组学谱，这表明可能的治疗靶向病变损伤部位。HBD 2没有显示出任何直接的蛋白酶抑制或诱导已知抗蛋白酶的表达，没有改变角质形成细胞的迁移或增殖，或形成保护性纳米网结构。这些数据验证了HBD 2在体外的屏障保护特性，并建立了关键蛋白质数据集以进行进一步的靶向机制分析。
The human skin barrier, a biological imperative, is impaired in inflammatory skin diseases such as atopic dermatitis (AD). Staphylococcus aureus is associated with AD lesions and contributes to pathological inflammation and further barrier impairment. S. aureus secretes extracellular proteases, such as V8 (or ‘SspA’), which cleave extracellular proteins to reduce skin barrier. Previous studies demonstrated that the host defence peptide human beta-defensin 2 (HBD2) prevented V8-mediated damage. Here, the mechanism of HBD2-mediated barrier protection in vitro is examined. Application of exogenous HBD2 provided protection against V8, irrespective of timeline of application or native peptide folding, raising the prospect of simple peptide analogues as therapeutics. HBD2 treatment, in context of V8-mediated damage, modulated the proteomic/secretomic profiles of HaCaT cells, altering levels of specific extracellular matrix proteins, potentially recovering V8 damage. However, HBD2 alone did not substantially modulate cellular proteomic/secretomics profiles in the absence of damage, suggesting possible therapeutic targeting of lesion damage sites only. HBD2 did not show any direct protease inhibition or induce expression of known antiproteases, did not alter keratinocyte migration or proliferation, or form protective nanonet structures. These data validate the barrier-protective properties of HBD2 in vitro and establish key protein datasets for further targeted mechanistic analyses.
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影响因子：
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