糖尿病和湿疹（eczema）表面上看来是完全无关的两种疾病，不过美国加州大学圣地亚哥分校的生物学家近日发现，这二者之间存在着一个至关重要的生物化学联系。
圣地亚哥分校生物学家Colin Jamora和同事报告说，他们发现先前被认为只与细胞死亡有关的蛋白caspase 8，在实验小鼠的伤口愈合方面发挥着关键性的作用。引人注意的是，caspase 8在湿疹患者体内表达不足，而在糖尿病患者体内则过度表达。相关论文将发表在3月26日的《自然》（Nature）杂志上。
研究人员表示，他们的发现可能解释了为什么糖尿病患者在面对微小伤口时，会缺乏正常的伤应，并因此遭受严重的并发症；以及为什么湿疹患者的皮肤会出现慢性炎症，从而危及它的保护功能。
Jamora说：“caspase 8的缺失会刺激发炎，产生大量细胞阻止细菌感染伤口。它还会刺激一些干细胞的产生，这些干细胞提供一些材料帮助愈合伤口。这很重要，因为在伤口的最初阶段，皮肤的保护层被破坏，内在机体均暴露于细菌和环境毒素。”
Jamora目前和同事正在研究糖尿病的实验鼠模型，以确定人工阻尼caspase 8的产生是否会恢复它们愈合伤口的能力。同时，Jamora说：“我们也在用caspase-8敲除小鼠作为模型系统来研究湿疹，以确定各种病理要素，并借此揭示该病新的靶标，为全世界患有该病的10%至20%的儿童造福。”（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 8 February 2009 | doi:10.1038/nature07687
Dynamic expression of epidermal caspase 8 simulates a wound healing response
Pedro Lee1, Dai-Jen Lee1, Carol Chan1, Shih-Wei Chen1, Irene Ch'en2 & Colin Jamora1,3
1 Section of Cell and Developmental Biology, Division of Biological Sciences, Natural Science Building, Room 6311, 9500 Gilman Drive, MC 0380
2 Section of Molecular Biology, Division of Biological Sciences, Natural Science Building, Room 5116, 9500 Gilman Drive, MC 0377
3 Department of Medicine (Dermatology), Natural Science Building, Room 6113, 9500 Gilman Drive, MC 0380, La Jolla, California 92093, USA
Correspondence to: Colin Jamora1,3 Correspondence and requests for materials should be addressed to C.J.
Tissue homeostasis and regeneration are regulated by an intricate balance of seemingly competing processes—proliferation versus differentiation, and cell death versus survival1. Here we demonstrate that the loss of epidermal caspase 8, an important mediator of apoptosis2, recapitulates several phases of a wound healing response in the mouse. The epidermal hyperplasia in the caspase 8 null skin is the culmination of signals exchanged between epidermal keratinocytes, dermal fibroblasts and leukocytic cells. This reciprocal interaction is initiated by the paracrine signalling of interleukin 1 (IL1), which activates both skin stem cell proliferation and cutaneous inflammation. The non-canonical secretion of IL1 is induced by a p38-MAPK-mediated upregulation of NALP3 (also known as NLRP3), leading to inflammasome assembly and caspase 1 activation. Notably, the increased proliferation of basal keratinocytes is counterbalanced by the growth arrest of suprabasal keratinocytes in the stratified epidermis by IL1-dependent NFB signalling. Altogether, our findings illustrate how the loss of caspase 8 can affect more than programmed cell death to alter the local microenvironment and elicit processes common to wound repair and many neoplastic skin disorders.
