Efficient Keratinocyte Differentiation Strictly Depends on JNK-Induced Soluble Factors in Fibroblasts
| Autor: | Nevisa Caushaj, Bettina Hartenstein, Stefan Holland-Cunz, Marina Schorpp-Kistner, Jochen Hess, Sibylle Szabowski, Erwin F. Wagner, Zbigniew Rogon, Roland Eils, Sebastian Baars, Marion Schumacher, Christine Bauer, Christian Schuster, Peter Angel, Tobias Bauer |
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| Jazyk: | angličtina |
| Předmět: |
Keratinocytes
MAP Kinase Signaling System Cellular differentiation Primary Cell Culture Dermatology Biology Biochemistry Transcriptome Paracrine signalling Mice medicine Animals Humans Mitogen-Activated Protein Kinase 9 Mitogen-Activated Protein Kinase 8 Fibroblast Molecular Biology Cell Line Transformed Mice Knockout Wound Healing Epidermis (botany) integumentary system Cell Differentiation Cell Biology Fibroblasts Coculture Techniques Cell biology medicine.anatomical_structure Epidermal Cells Solubility Signal transduction Epidermis Keratinocyte Wound healing Signal Transduction |
| Zdroj: | Journal of Investigative Dermatology. (5):1332-1341 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2013.535 |
| Popis: | Previous studies demonstrated that fibroblast-derived and JUN-dependent soluble factors have a crucial role on keratinocyte proliferation and differentiation during cutaneous wound healing. Furthermore, mice with a deficiency in Jun N-terminal kinases (JNKs) , 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 used a heterologous coculture model combining primary human keratinocytes and murine fibroblasts. Although cocultured 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 is also critically dependent 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 coculture 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 has a pivotal role in the paracrine cross talk between dermal fibroblasts and epidermal keratinocytes during wound healing. |
| Databáze: | OpenAIRE |
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