Efficient keratinocyte differentiation strictly depends on JNK-induced soluble factors in fibroblasts

Marion Schumacher1, Christian Schuster1, Zbigniew M Rogon2

  • 1Division of Signal Transduction and Growth Control, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum, Heidelberg, Germany.

Insights

Mesenchymal Jun N-terminal kinases (JNKs) are crucial for skin healing. JNK signaling in fibroblasts supports keratinocyte differentiation through secreted factors, essential for effective wound closure.

Area of Science:

  • Dermatology
  • Wound Healing Research
  • Cell Signaling

Background:

  • Fibroblast-derived factors and JUN signaling influence keratinocyte proliferation and differentiation in skin wound healing.
  • Jun N-terminal kinases (JNKs) play a role in skin development and wound closure, as evidenced by studies in JNK-deficient mice.

Purpose of the Study:

  • To investigate the specific role of dermal Jun N-terminal kinases (JNKs) in regulating keratinocyte behavior during wound healing.
  • To elucidate the mechanisms by which fibroblasts influence keratinocyte differentiation via JNK signaling.

Main Methods:

  • Utilized a heterologous co-culture model with primary human keratinocytes and murine fibroblasts.
  • Employed temporal transcriptome analysis to monitor gene expression changes in differentiating keratinocytes.
  • Compared keratinocyte behavior with fibroblasts deficient in JNK1 and JNK2.

Main Results:

  • JNK1/JNK2-deficient fibroblasts did not impair keratinocyte proliferation but were essential for efficient keratinocyte differentiation.
  • Loss of JNK signaling in fibroblasts significantly altered the expression of secreted proteins.
  • Efficient keratinocyte terminal differentiation requires continuous JNK-dependent, fibroblast-derived soluble factors.

Conclusions:

  • Mesenchymal JNK signaling is pivotal for the paracrine communication between dermal fibroblasts and epidermal keratinocytes.
  • Fibroblast-derived soluble factors, regulated by JNK, are critical for keratinocyte differentiation during wound healing.
  • This study highlights a key molecular pathway in skin repair, involving fibroblast-mesenchyme-epidermis crosstalk.

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