CD44 regulates tight-junction assembly and barrier function.
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CD44 regulates tight-junction assembly and barrier function. / Kirschner, Nina; Haftek, Marek; Niessen, Carien M; Behne, Martin; Furuse, Mikio; Moll, Ingrid; Brandner, Johanna.
In: J INVEST DERMATOL, Vol. 131, No. 4, 4, 2011, p. 932-943.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - CD44 regulates tight-junction assembly and barrier function.
AU - Kirschner, Nina
AU - Haftek, Marek
AU - Niessen, Carien M
AU - Behne, Martin
AU - Furuse, Mikio
AU - Moll, Ingrid
AU - Brandner, Johanna
PY - 2011
Y1 - 2011
N2 - Upon barrier disturbance, adult CD44 knockout (KO) mice show delayed recovery of epidermal barrier function. This correlates with the loss of apical polarization of lamellar body (LB) secretion. As tight junctions (TJs) are crucial for barrier function and regulate polarized targeting of vesicles, we hypothesized that CD44 regulates TJs and associated cell polarity complexes, which in turn contributes to altered skin barrier function in CD44 KO mice. We show a delay in embryonic barrier formation associated with a loss of apical LB localization in CD44 KO mice, which correlates with alterations in TJ proteins and Par3. Simultaneously, the activity of Rac1, a major regulator of TJ barrier function, was reduced. Importantly, normalization of barrier function at E18.5 coincided with the recovery of these proteins. Tape-stripping experiments revealed that the loss of CD44 also affected TJ proteins upon induced disturbance of the barrier in adult mice. In CD44 KO keratinocytes, cell polarization and TJ barrier function were impaired. An alteration of differentiation markers was also observed, but was less pronounced than alterations of TJ proteins. Taken together, the results reveal an important function for CD44 in the assembly and function of TJs, suggesting their involvement in the skin barrier phenotype of CD44 KO mice.
AB - Upon barrier disturbance, adult CD44 knockout (KO) mice show delayed recovery of epidermal barrier function. This correlates with the loss of apical polarization of lamellar body (LB) secretion. As tight junctions (TJs) are crucial for barrier function and regulate polarized targeting of vesicles, we hypothesized that CD44 regulates TJs and associated cell polarity complexes, which in turn contributes to altered skin barrier function in CD44 KO mice. We show a delay in embryonic barrier formation associated with a loss of apical LB localization in CD44 KO mice, which correlates with alterations in TJ proteins and Par3. Simultaneously, the activity of Rac1, a major regulator of TJ barrier function, was reduced. Importantly, normalization of barrier function at E18.5 coincided with the recovery of these proteins. Tape-stripping experiments revealed that the loss of CD44 also affected TJ proteins upon induced disturbance of the barrier in adult mice. In CD44 KO keratinocytes, cell polarization and TJ barrier function were impaired. An alteration of differentiation markers was also observed, but was less pronounced than alterations of TJ proteins. Taken together, the results reveal an important function for CD44 in the assembly and function of TJs, suggesting their involvement in the skin barrier phenotype of CD44 KO mice.
M3 - SCORING: Journal article
VL - 131
SP - 932
EP - 943
JO - J INVEST DERMATOL
JF - J INVEST DERMATOL
SN - 0022-202X
IS - 4
M1 - 4
ER -