Thrombospondin-4 Is a Soluble Dermal Inflammatory Signal That Selectively Promotes Fibroblast Migration and Keratinocyte Proliferation for Skin Regeneration and Wound Healing

Frontiers in Cell and Developmental Biology

Esko Kankuri¹  Heli Lagus²  Viljar Jaks³  Külli Kingo³  Claudia Griselda Cárdenas-León⁴  Mariliis Klaas⁴  Kristina Mäemets-Allas⁴  Elizabeth Heinmäe⁴  Terje Arak⁵  Mart Eller⁵ 

[1] Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland;Department of Plastic Surgery and Wound Healing Centre, Helsinki University Hospital, University of Helsinki, Helsinki, Finland;Dermatology Clinic, Tartu University Hospital, Tartu, Estonia;Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia;Surgery Clinic, Tartu University Hospital, Tartu, Estonia;

关键词: skin regeneration;    wound healing;    burns;    thrombospondin-4;    fibroblasts;    psoriasis;   

DOI  :  10.3389/fcell.2021.745637

来源: DOAJ

【 摘 要 】

Thrombospondin-4 (THBS4) is a non-structural extracellular matrix molecule associated with tissue regeneration and a variety of pathological processes characterized by increased cell proliferation and migration. However, the mechanisms of how THBS4 regulates cell behavior as well as the pathways contributing to its effects have remained largely unexplored. In the present study we investigated the role of THBS4 in skin regeneration both in vitro and in vivo. We found that THBS4 expression was upregulated in the dermal compartment of healing skin wounds in humans as well as in mice. Application of recombinant THBS4 protein promoted cutaneous wound healing in mice and selectively stimulated migration of primary fibroblasts as well as proliferation of keratinocytes in vitro. By using a combined proteotranscriptomic pathway analysis approach we discovered that β-catenin acted as a hub for THBS4-dependent cell signaling and likely plays a key role in promoting its downstream effects. Our results suggest that THBS4 is an important contributor to wound healing and its incorporation into novel wound healing therapies may be a promising strategy for treatment of cutaneous wounds.

【 授权许可】

Unknown