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Efficient Keratinocyte Differentiation Strictly Depends on JNK-Induced Soluble Factors in Fibroblasts.
MedLine Citation:
PMID:  24335928     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Previous studies demonstrated that fibroblast-derived and JUN-dependent soluble factors play a crucial role on keratinocyte proliferation and differentiation during cutaneous wound healing. Furthermore, mice with a deficiency in Jun N-terminal kinases, JNK1 or JNK2, showed impaired skin development and delayed wound closure. To decipher the role of dermal JNK in keratinocyte behavior during these processes we employed a heterologous co-culture model combining primary human keratinocytes and murine fibroblasts. While co-cultured JNK1/JNK2-deficient fibroblasts did not affect keratinocyte proliferation, temporal monitoring of the transcriptome of differentiating keratinocytes revealed that efficient keratinocyte differentiation not only requires the support by fibroblast-derived soluble factors but critically depends on JNK1 and JNK2 signaling in these cells. Moreover, we showed that the repertoire of fibroblast transcripts encoding secreted proteins is severely disarranged upon loss of JNK under the co-culture conditions applied. Finally, our data demonstrate that efficient keratinocyte terminal differentiation requires constant presence of JNK-dependent and fibroblast-derived soluble factors. Taken together, our results imply that mesenchymal JNK plays a pivotal role in the paracrine crosstalk between dermal fibroblasts and epidermal keratinocytes during wound healing.Journal of Investigative Dermatology accepted article preview online, 16 December 2013. doi:10.1038/jid.2013.535.
Authors:
Marion Schumacher; Christian Schuster; Zbigniew M Rogon; Tobias Bauer; Nevisa Caushaj; Sebastian Baars; Sibylle Szabowski; Christine Bauer; Marina Schorpp-Kistner; Jochen Hess; Stefan Holland-Cunz; Erwin F Wagner; Roland Eils; Peter Angel; Bettina Hartenstein
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-12-16
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  -     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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