Abstract
The cornified layer, the stratum corneum, of the epidermis is an efficient barrier to the passage of genetic material, i.e. nucleic acids. It contains enzymes that degrade RNA and DNA which originate from either the living part of the epidermis or from infectious agents of the environment. However, the molecular identities of these nucleases are only incompletely known at present. Here we performed biochemical and genetic experiments to determine the main DNase activity of the stratum corneum. DNA degradation assays and zymographic analyses identified the acid endonucleases L-DNase II, which is derived from serpinB1, and DNase 2 as candidate DNases of the cornified layer of the epidermis. siRNA-mediated knockdown of serpinB1 in human in vitro skin models and the investigation of mice deficient in serpinB1a demonstrated that serpinB1-derived L-DNase II is dispensable for epidermal DNase activity. By contrast, knockdown of DNase 2, also known as DNase 2a, reduced DNase activity in human in vitro skin models. Moreover, the genetic ablation of DNase 2a in the mouse was associated with the lack of acid DNase activity in the stratum corneum in vivo. The degradation of endogenous DNA in the course of cornification of keratinocytes was not impaired by the absence of DNase 2. Taken together, these data identify DNase 2 as the predominant DNase on the mammalian skin surface and indicate that its activity is primarily targeted to exogenous DNA.
Highlights
The outermost layer of the epidermis, i.e. the stratum corneum, is an important barrier of the body to the environment [1,2]
This study shows that the stratum corneum contains, besides other minor DNase activities, one predominant DNase activity
Rigorous genetic testing of two candidate acid DNases, i.e. DNase 2 and L-DNase II, demonstrated that DNase 2 plays a nonredundant role as the main DNase of the mammalian stratum corneum whereas L-DNase II is dispensable for the acid DNase activity in the stratum corneum
Summary
The outermost layer of the epidermis, i.e. the stratum corneum, is an important barrier of the body to the environment [1,2]. It has been proposed that the DNases of the stratum corneum have a primary function in the degradation of endogenous DNA during cornification of keratinocytes [6]. These DNases may play a role in the defense against infectious agents containing genetic information encoded by DNA such as papilloma viruses or bacteria that utilize extracellular DNA for biofilm formation [7]. In spite of the long history of research on epidermal DNases, the molecular identities of DNases in the epidermis and in the stratum corneum have remained largely unknown
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