title: Expression and regulation of murine SPINK12, a potential orthologue of human LEKTI2.
abstract: A balanced proteolytic activity in the epidermis is vital to maintain epidermal homoeostasis and barrier function. Distinct protease-inhibitor systems are operating in different epidermal layers. In the uppermost layer, the stratum corneum, kallikrein-like proteases and their inhibitors are responsible for desquamation of the cornified keratinocytes, thus regulating the integrity of the epidermal barrier. Following discovery and characterisation of the human multidomain inhibitor LEKTI (lympho-epithelial Kazal-type-related inhibitor, encoded by hspink5), several new members of the Kazal-type inhibitor family have been identified. Here we describe expression and regulation of murine SPINK12, a potential orthologue of human LEKTI2. Its expression was analysed by RT-PCR and immunohistochemistry revealing organ-specific pattern with high level of expression in the epidermis and several epithelia including the stomach, kidney and uterus. In addition, mSPINK12 expression in the epidermis of skin at footpads, where stratification is markedly pronounced, was several folds higher than in the abdominal epidermis. mSPINK12 mRNA levels were not affected by any cytokines tested while treatment of primary murine keratinocytes with the combination of calcium and sorbitol resulted in a strong increase in its mRNA. It appears that mspink12 is especially expressed in the epidermal areas with thick skin and that its regulation generally responds to differentiation signals. mrSPINK12 shows an inhibitory activity against murine keratinocyte-derived trypsin-like proteolytic activity, thus, the protein does appear orthologous to human LEKTI2 and may play an role in the regulation of epithelial cell functions.
authors: Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: Karina
authors: K
authors: Reiss
authors: Ulf
authors: U
authors: Meyer-Hoffert
authors: Jan
authors: J
authors: Fischer
authors: Maria
authors: M
authors: Sperrhacke
authors: Zhihong
authors: Z
authors: Wu
authors: Olga
authors: O
authors: Dimitrieva
authors: Pavel
authors: P
authors: Krenek
authors: Sarka
authors: S
authors: Suchanova
authors: Halka
authors: H
authors: Buryova
authors: Rena
authors: R
authors: Brauer
authors: Radislav
authors: R
authors: Sedlacek
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074162:Serine Peptidase Inhibitors, Kazal Type; D012867:Skin / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D018076:DNA, Complementary; D053491:Proteinase Inhibitory Proteins, Secretory; D011994:Recombinant Proteins; D000074162:Serine Peptidase Inhibitors, Kazal Type; C570395:SPINK12 protein, mouse; C542011:SPINK9 protein, human