Epidermal-specific deletion of CD44 reveals a function in keratinocytes in response to mechanical stress

• Published in: Cell death & disease Vol. 7; no. 11; p. e2461
• Main Authors: Shatirishvili, M, Burk, A S, Franz, C M, Pace, G, Kastilan, T, Breuhahn, K, Hinterseer, E, Dierich, A, Bakiri, L, Wagner, E F, Ponta, H, Hartmann, T N, Tanaka, M, Orian-Rousseau, V
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10-11-2016; Springer Nature B.V; Nature Publishing Group
• Subjects: 38; 45; 631/45/612/1231; 631/67/1813; 631/80/86/2366; 64; 64/60; 692/1807/1812; Animals; Antibodies; Biochemistry; Biochemistry, Molecular Biology; Biomedical and Life Sciences; Cell Adhesion - drug effects; Cell Biology; Cell Culture; Cell Differentiation - drug effects; Cell Movement - drug effects; Cell Proliferation - drug effects; Epidermis - metabolism; Gene Deletion; Homeostasis - drug effects; Hyaluronan Receptors - metabolism; Hyaluronic Acid - pharmacology; Immunology; Keratinocytes - drug effects; Keratinocytes - metabolism; Keratins - metabolism; Life Sciences; Membranes; Mice, Knockout; Organ Specificity - drug effects; Original; original-article; Proteins; Skin; Skin - metabolism; Stress; Stress, Mechanical; Wound Healing - drug effects
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2016.342

CD44, a large family of transmembrane glycoproteins, plays decisive roles in physiological and pathological conditions. CD44 isoforms are involved in several signaling pathways essential for life such as growth factor-induced signaling by EGF, HGF or VEGF. CD44 is also the main hyaluronan (HA) receptor and as such is involved in HA-dependent processes. To allow a genetic dissection of CD44 functions in homeostasis and disease, we generated a
Cd44
floxed allele allowing tissue- and time-specific inactivation of all CD44 isoforms
in vivo
. As a proof of principle, we inactivated
Cd44
in the skin epidermis using the
K14Cre
allele. Although the skin of such
Cd44
Δker
mutants appeared morphologically normal, epidermal stiffness was reduced, wound healing delayed and TPA induced epidermal thickening decreased. These phenotypes might be caused by cell autonomous defects in differentiation and HA production as well as impaired adhesion and migration on HA by
Cd44
Δker
keratinocytes. These findings support the usefulness of the conditional
Cd44
allele in unraveling essential physiological and pathological functions of CD44 isoforms.