Chronic inflammation imposes aberrant cell fate in regenerating epithelia through mechanotransduction View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12-21

AUTHORS

Craig S. Nowell, Pascal D. Odermatt, Luca Azzolin, Sylke Hohnel, Erwin F. Wagner, Georg E. Fantner, Matthias P. Lutolf, Yann Barrandon, Stefano Piccolo, Freddy Radtke

ABSTRACT

Chronic inflammation is associated with a variety of pathological conditions in epithelial tissues, including cancer, metaplasia and aberrant wound healing. In relation to this, a significant body of evidence suggests that aberration of epithelial stem and progenitor cell function is a contributing factor in inflammation-related disease, although the underlying cellular and molecular mechanisms remain to be fully elucidated. In this study, we have delineated the effect of chronic inflammation on epithelial stem/progenitor cells using the corneal epithelium as a model tissue. Using a combination of mouse genetics, pharmacological approaches and in vitro assays, we demonstrate that chronic inflammation elicits aberrant mechanotransduction in the regenerating corneal epithelium. As a consequence, a YAP–TAZ/β-catenin cascade is triggered, resulting in the induction of epidermal differentiation on the ocular surface. Collectively, the results of this study demonstrate that chronic inflammation and mechanotransduction are linked and act to elicit pathological responses in regenerating epithelia. More... »

PAGES

168-180

Journal

TITLE

Nature Cell Biology

ISSUE

2

VOLUME

18

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncb3290

DOI

http://dx.doi.org/10.1038/ncb3290

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1011115626

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26689676


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50 schema:description Chronic inflammation is associated with a variety of pathological conditions in epithelial tissues, including cancer, metaplasia and aberrant wound healing. In relation to this, a significant body of evidence suggests that aberration of epithelial stem and progenitor cell function is a contributing factor in inflammation-related disease, although the underlying cellular and molecular mechanisms remain to be fully elucidated. In this study, we have delineated the effect of chronic inflammation on epithelial stem/progenitor cells using the corneal epithelium as a model tissue. Using a combination of mouse genetics, pharmacological approaches and in vitro assays, we demonstrate that chronic inflammation elicits aberrant mechanotransduction in the regenerating corneal epithelium. As a consequence, a YAP–TAZ/β-catenin cascade is triggered, resulting in the induction of epidermal differentiation on the ocular surface. Collectively, the results of this study demonstrate that chronic inflammation and mechanotransduction are linked and act to elicit pathological responses in regenerating epithelia.
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57 aberrant wound healing
58 aberrations
59 acts
60 approach
61 body
62 cancer
63 cascade
64 cell fate
65 cell function
66 cells
67 chronic inflammation
68 combination
69 conditions
70 consequences
71 corneal epithelium
72 differentiation
73 disease
74 effect
75 epidermal differentiation
76 epithelial stem
77 epithelial stem/progenitor cells
78 epithelial tissues
79 epithelium
80 evidence
81 factors
82 fate
83 function
84 genetics
85 healing
86 induction
87 inflammation
88 inflammation-related diseases
89 mechanism
90 mechanotransduction
91 metaplasia
92 model tissue
93 molecular mechanisms
94 mouse genetics
95 ocular surface
96 pathological conditions
97 pathological response
98 pharmacological approaches
99 progenitor cell function
100 progenitor cells
101 relation
102 response
103 results
104 significant body
105 stem
106 stem/progenitor cells
107 study
108 surface
109 tissue
110 variety
111 wound healing
112 β-catenin cascade
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