Muco-ciliary differentiation of nasal epithelial cells is decreased after wound healing in vitro.
BACKGROUND
Epithelial damage and modifications of cell differentiation are frequent in airway diseases with chronic inflammation, in which transforming growth factor-beta1 (TGF-beta1) plays an important role. The aim of this study was to evaluate the differentiation of human nasal epithelial cells (HNEC) after wound healing and the potential effects of TGF-beta1.


METHODS
Basal, mucus, and ciliated cells were characterized by cytokeratin-14, MUC5AC, and betaIV tubulin immunodetection, respectively. Their expression was evaluated in situ in nasal polyps and in an in vitro model of wound healing in primary cultures of HNEC after wound closure, under basal conditions and after TGF-beta1 supplementation. Using RT-PCR, the effects of TGF-beta1 on MUC5AC and DNAI1 genes, specifically transcribed in mucus and ciliated cells, were evaluated.


RESULTS
In situ, high TGF-beta1 expression was associated with low MUC5AC and betaIV tubulin expression. In vitro, under basal conditions, MUC5AC expression remained stable, cytokeratin-14 expression was strong and decreased with time, while betaIV tubulin expression increased. Transforming growth factor-beta1 supplementation downregulated MUC5AC and betaIV tubulin expression as well as MUC5AC and DNAI1 transcripts.


CONCLUSIONS
After a wound, differentiation into mucus and ciliated cells was possible and partially inhibited in vitro by TGF-beta1, a cytokine that may be involved in epithelial remodeling observed in chronic airway diseases.
Lazard
D S
DS
INSERM U955 and Université Paris 12, Créteil, Hôpital Armand-Trousseau, Paris, France.
Moore
A
A
Hupertan
V
V
Martin
C
C
Escabasse
V
V
Dreyfus
P
P
Burgel
P-R
PR
Amselem
S
S
Escudier
E
E
Coste
A
A
D056444:Axonemal Dyneins; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism; D015536:Down-Regulation; D004398:Dyneins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D053547:Keratin-14 / Q000378:metabolism; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism; D009077:Mucins / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology* / Q000378:metabolism; D009298:Nasal Polyps / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism; D014945:Wound Healing
C425071:DNAI1 protein, human; D053547:Keratin-14; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; C409879:TUBB7P protein, human; D053773:Transforming Growth Factor beta1; D014404:Tubulin; D056444:Axonemal Dyneins; D004398:Dyneins