@article{Kobiela:2026:10.1186/s12915-025-02499-y,
author = {Kobiela, A and Klimczuk, M and Serafin, PK and Kitowska, K and Biernacka, A and Abouali, R and de, la Serna JB and Wang, X and Gajdowska, F and Kosobucka, A and Siedlar, AM and Hauer, A and Hovhannisyan, L and Bogucka, A and Smits, JPH and van, den Bogaard EH and Sdej, R and Ogg, GS and Gutowska-Owsiak, D},
doi = {10.1186/s12915-025-02499-y},
journal = {BMC Biology},
title = {Remodeling of the cell membrane-associated protein pool affects adhesive membrane properties in filaggrin insufficient keratinocytes and impacts distinct cellular and organellar functions},
url = {http://dx.doi.org/10.1186/s12915-025-02499-y},
year = {2026}
}

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TY  - JOUR
AB  - BackgroundAtopic dermatitis (AD) is a highly prevalent inflammatory skin disease, affecting up to 30% of children at some point in their life and frequently persisting into adulthood. Insufficiency in the late epidermal protein filaggrin is frequently observed in the lesional skin of patients, with direct and indirect impact on the skin barrier quality and function. We hypothesized that filaggrin reduction influences intracellular, surface, and derived extracellular membranes of keratinocytes with multiple impacts on the cell function.ResultsUsing filaggrin knockdown keratinocytes generated by shRNA interference (shFLG), we determined that the physical characteristics of the cellular membranes (reported by refractive index) are changed on a filaggrin insufficiency background. Using proteomics, protein binding modeling, and functional assays, we established that filaggrin insufficiency in keratinocytes results in changes in both organelles comprised of internal cellular membranes (i.e., small extracellular vesicles, sEVs) and the plasma membrane. We detected increased association of anti-adhesive proteins (tenascin-C and matrilin-2) with sEVs, resulting in a reduction of the fibronectin-1-mediated sEV uptake by dendritic cell subsets. At the same time, dysregulation of the tight junction and cell adhesion molecules at the level of the cell increased keratinocyte adhesiveness to reconstituted basement membrane substratum as well as faster gap closure in the wound healing assay. We also independently confirmed the findings on sEV uptake and wound healing in filaggrin knockout N/TERT-2G keratinocytes, which more closely resemble primary cells.ConclusionsWe conclude that the alterations in different membrane compartments in filaggrin insufficiency are reflected in changes in keratinocyte functions of relevance to AD pathology, and strategies to target those could open up new therapeutic approaches.
AU  - Kobiela,A
AU  - Klimczuk,M
AU  - Serafin,PK
AU  - Kitowska,K
AU  - Biernacka,A
AU  - Abouali,R
AU  - de,la Serna JB
AU  - Wang,X
AU  - Gajdowska,F
AU  - Kosobucka,A
AU  - Siedlar,AM
AU  - Hauer,A
AU  - Hovhannisyan,L
AU  - Bogucka,A
AU  - Smits,JPH
AU  - van,den Bogaard EH
AU  - Sdej,R
AU  - Ogg,GS
AU  - Gutowska-Owsiak,D
DO  - 10.1186/s12915-025-02499-y
PY  - 2026///
SN  - 1741-7007
TI  - Remodeling of the cell membrane-associated protein pool affects adhesive membrane properties in filaggrin insufficient keratinocytes and impacts distinct cellular and organellar functions
T2  - BMC Biology
UR  - http://dx.doi.org/10.1186/s12915-025-02499-y
UR  - https://doi.org/10.1186/s12915-025-02499-y
ER  - 

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