Lympho-epithelial Kazal-type related inhibitor 2 (LEKTI-2) is a protein encoded by the ''SPINK9'' gene in humans. ''SPINK9'' is a member of a gene family cluster located on
chromosome 5q33.1, which includes ''
SPINK5'' and ''
SPINK6''.
LEKTI-2 is an inhibitor of
KLK5.
Desquamation
The outer layer of the
epidermis
The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the ...
is called the
stratum corneum
The stratum corneum (Latin language, Latin for 'horny layer') is the outermost layer of the epidermis (skin), epidermis. Consisting of dead tissue, it protects underlying tissue from infection, dehydration, chemicals and mechanical stress. It is ...
. In the stratum corneum terminally differentiated corneocytes are held together by corneodesmosomes. In order for
desquamation
Desquamation, or peeling skin, is the shedding of dead cells from the outermost layer of skin.
The term is .
Physiologic desquamation
Keratinocytes are the predominant cells of the epidermis, the outermost layer of the skin. Living keratin ...
to occur, corneodesmosomes need to be fully degraded.
KLK5 and
KLK7
Kallikrein-related peptidase 7 (KLK7) is a serine protease that in humans is encoded by the ''KLK7'' gene. KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme (SCCE). It was later identified as ...
are two serine proteases that degrade corneodesmosomes. LEKTI-2 regulates corneodesmosome degradation by inhibiting KLK5. In acral (palm and sole) skin, where desquamation needs to be delayed, ''SPINK9'' expression is strongly upregulated.
The resulting high level of LEKTI-2 delays corneodesmosome degradation, thereby allowing the epidermis to form a thick protective stratum corneum layer.
Clinical Significance
SPINK9 is overexpressed in
lichen simplex chronicus,
actinic keratosis
Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis, is a Premalignant condition, pre-cancerous area of thick, scaly, or crusty skin.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed. ...
, and
squamous cell carcinoma
Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
.
See also
*
Kazal-type serine protease inhibitor domain
References
Proteins
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