SPINK7 gene

SPINK is the acronym for "Serine Peptidase Inhibitor Kazal" and comprises a gene family located on different chromosomes. The members of this gene family code for specific protease inhibitors, the SPINK protease inhibitor Kazal-type (SPINK) family. These are serine peptidase inhibitors.

They contain at least one inhibitory Kazal domain. This domain binds to its targets, the serine proteases, and inhibits their proteolytic functions. This regulatory inhibitory function and its fine-tuning is of fundamental importance for many epithelia.

SPINK7 is located on chromosome 5q32 and codes for a protein of the same name, the serine peptidase inhibitor Kazal type 7. SPINK7 has previously been described as a cancer-relevant gene in the oesophagus. However, it is also expressed in healthy human skin. In addition, SPINK7 is upregulated in inflammatory skin diseases such as psoriasis and eczema (Weber C et al. 2017).

SPINK7 has been shown to be part of the differentiation program of the human esophageal epithelium. The absence of SPINK7 in the epithelial cells of the oesophagus appears to lead to a dysfunction of the epithelial barrier in humans (Lyles J et al. 2019).SPINK7 (as well as SPINK5) is only expressed to a small extent in eosinophilic oesophagitis. Its depletion is of pathogenetic relevance for eosinophilic oesophagitis (Azouz NP et al.(2018). Apparently, the loss of cellular differentiation and the altered gene expression lead to an allergic immune reaction.

Furthermore, epithelial silencing of SPINK7 promotes the production of proinflammatory cytokines, including thymic stromal lymphopoietin(TSLP). Loss of SPINK7 increased the activity of urokinase plasminogen-type activator (uPA) (Azouz NP et al. 2018).

1. Azouz NP et al.(2018) The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses. Sci Transl Med 10:eaap9736.
2. Lyles J et al.(2019) Role of genetics, environment, and their interactions in the pathogenesis of eosinophilic esophagitis. Curr Opin Immunol 60:46-53.
3. Weber C et al. (2017) The serine protease inhibitor of Kazal-type 7 (SPINK7) is expressed in human skin. Arch Dermatol Res 309:767-771.
4. Xue C et al (2019) Elevated SPINK2 gene expression is a predictor of poor prognosis in acute myeloid leukemia. Oncol Lett 18:2877-2884.
5. Wapenaar MC et al (2007) The SPINK-gene family. Immunogenetics 59: 349-357