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. 2023 Jan 22;24(3):2193.
doi: 10.3390/ijms24032193.

Transglutaminase Activity Is Conserved in Stratified Epithelia and Skin Appendages of Mammals and Birds

Attila Placido Sachslehner  1 , Marta Surbek  1 , Bahar Golabi  1 , Miriam Geiselhofer  1 , Karin Jäger  1 , Claudia Hess  2 , Ulrike Kuchler  3 , Reinhard Gruber  3 , Leopold Eckhart  1
Affiliations

Transglutaminase Activity Is Conserved in Stratified Epithelia and Skin Appendages of Mammals and Birds

Attila Placido Sachslehner et al. Int J Mol Sci. .

Abstract

The cross-linking of structural proteins is critical for establishing the mechanical stability of the epithelial compartments of the skin and skin appendages. The introduction of isopeptide bonds between glutamine and lysine residues depends on catalysis by transglutaminases and represents the main protein cross-linking mechanism besides the formation of disulfide bonds. Here, we used a fluorescent labeling protocol to localize the activity of transglutaminases on thin sections of the integument and its appendages in mammals and birds. In human tissues, transglutaminase activity was detected in the granular layer of the epidermis, suprabasal layers of the gingival epithelium, the duct of sweat glands, hair follicles and the nail matrix. In the skin appendages of chickens, transglutaminase activity was present in the claw matrix, the feather follicle sheath, the feather sheath and in differentiating keratinocytes of feather barb ridges. During chicken embryogenesis, active transglutaminase was found in the cornifying epidermis, the periderm and the subperiderm. Transglutaminase activity was also detected in the filiform papillae on the tongue of mice and in conical papillae on the tongue of chickens. In summary, our study reveals that transglutaminase activities are widely distributed in integumentary structures and suggests that transglutamination contributes to the cornification of hard skin appendages such as nails and feathers.

Keywords: chicken; cornification; eccrine gland; enzyme activity labeling; epidermis; evolution; feather; filiform papillae; gingiva; keratinocytes; nail; sweat gland; transglutaminase.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Transglutaminase (TGM) activity in the epidermis and gingival epithelium. (A) TGM activity (red) in the human epidermis. A membrane-associated signal was detected in the outermost nucleated cell layer of the epidermis. (B) In negative control experiments, CaCl2 was replaced with 5 mM EDTA. (C) TGM activity in the human gingiva. A membrane-associated signal was detected in several layers above the basal layer and in the outmost layer. (D) In negative control experiments, CaCl2 was replaced with 5 mM EDTA. (E) TGM activity in the sole skin of a rat. (F) In negative control experiments, CaCl2 was replaced with 5 mM EDTA. Dashed lines indicate the basement membrane. Continuous lines indicate the surface of the skin. der, dermis; epi, epidermis; lam, lamina propria; sc, stratum corneum. Scale bars: 50 µm (A,B,E,F), 100 µm (C,D).
Figure 2
Figure 2
Transglutaminase (TGM) activity in the tongue of mouse and chicken. (A) TGM activity (red) in the mouse tongue epithelium and in the filiform papillae. The section is slightly oblique. (B) Negative control in which CaCl2 was replaced by 5 mM EDTA. (C) TGM activity in an embryonic chicken tongue epithelium and in the conical papillae. (D) Negative control in which CaCl2 was replaced by 5 mM EDTA. Dashed lines indicate the basement membrane. cp, conical papilla; epi, epithelium; lam, lamina propria; fp, filiform papilla. Scale bars: 50 µm (A,B), 100 µm (C,D).
Figure 3
Figure 3
Transglutaminase (TGM) activity in the human nail matrix. (A) TGM activity (red) in the human nail. The nail matrix shows TGM activity and a membrane associated signal. (B,D) In negative control experiments CaCl2 was replaced by 5 mM EDTA. (C) Detail of the human nail matrix. Dashed lines indicate the basement membrane. epo, eponychium. An asterisk indicates a fold in the section due to a preparation artifact. Scale bars: 100 µm (A,B), 50 µm (C,D).
Figure 4
Figure 4
Transglutaminase (TGM) activity in the sweat gland duct. (A) TGM activity in the arcosyringium of a sweat gland in human skin. (B) Negative control in which CaCl2 was replaced by 5 mM EDTA. (C) TGM activity in the arcosyringium of a sweat gland in mouse sole skin. Asterisks indicate TGM activity present in corneocytes of the stratum corneum (sc). (D) Negative control in which CaCl2 was replaced by 5 mM EDTA. Der, dermis; epi, epidermis; sc, stratum corneum. Scale bars: 50 µm.
Figure 5
Figure 5
Transglutaminase (TGM) activity in feather follicles. (A) TGM activity (red) in a longitudinal (long.) section through a feather follicle. The white box indicates the area depicted at larger magnifications in panels (B,C). A black asterisk indicates an unspecifically labeled spot on the slide. (B,C) TGM activity in the developing feather barbules. (D,E) Negative control in which CaCl2 was replaced by 5 mM EDTA. (F) TGM activity in a cross-section of a feather follicle and the surrounding follicle sheath. (G) TGM activity in a cross-section of a feather follicle, merged with differential interference (phase) contrast. The mature cornified epithelium (white asterisk) lacks TGM activity. (H) Negative control to panel (F) in which CaCl2 was replaced by 5 mM EDTA. Scale bars: 500 µm (A), 50 µm (B,D,F–H), 20 µm (C,E).
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References

    1. Bereiter-Hahn J., Matoltsy A.G., Richards K.S., editors. Biology of the Integument. Vol 2. Vertebrates. Springer; New York, NY, USA: 1986.
    1. Chuong C.M., Nickoloff B.J., Elias P.M., Goldsmith L.A., Macher E., Maderson P.A., Sundberg J.P., Tagami H., Plonka P.M., Thestrup-Pederson K., et al. What is the ‘true’ function of skin? Exp. Dermatol. 2002;11:159–187. doi: 10.1034/j.1600-0625.2002.00112.x. - DOI - PMC - PubMed
    1. Candi E., Schmidt R., Melino G. The cornified envelope: A model of cell death in the skin. Nat. Rev. Mol. Cell. Biol. 2005;6:328–340. doi: 10.1038/nrm1619. - DOI - PubMed
    1. Eckhart L., Lippens S., Tschachler E., Declercq W. Cell death by cornification. Biochim. Biophys. Acta. 2013;1833:3471–3480. doi: 10.1016/j.bbamcr.2013.06.010. - DOI - PubMed
    1. Harland D.P., Plowman J.E. Development of hair fibres. Adv. Exp. Med. Biol. 2018;1054:109–154. doi: 10.1007/978-981-10-8195-8_10. - DOI - PubMed

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