Proteomics

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Thrombospondin-4 is a soluble dermal signal that selectively promotes fibroblast migration and keratinocyte proliferation for skin regeneration and wound healing


ABSTRACT: Thrombosponin-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 behaviour 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 recombinand 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 proteotranstriptomic pathway analysis approach we discovered that beta-catenin acted as a hub for THBS4-dependent cell signaling and likely plays a key role in promoting its downstream effects. Out 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 hard-to-heal wounds.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skin, Fibroblast

DISEASE(S): Wounds And Injuries

SUBMITTER: Viljar Jaks  

LAB HEAD: Viljar Jaks

PROVIDER: PXD027364 | Pride | 2022-02-17

REPOSITORIES: Pride

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Publications

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

Klaas Mariliis M   Mäemets-Allas Kristina K   Heinmäe Elizabeth E   Lagus Heli H   Cárdenas-León Claudia Griselda CG   Arak Terje T   Eller Mart M   Kingo Külli K   Kankuri Esko E   Jaks Viljar V  

Frontiers in cell and developmental biology 20210923


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 <i>in vitro</i> and <i>in vivo</i>. We found that THBS4 expr  ...[more]

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