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

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Klaas , M , Mäemets-Allas , K , Heinmäe , E , Lagus , H , Cardenas-Leon , C G , Arak , T , Eller , M , Kingo , K , Kankuri , E & Jaks , V 2021 , ' 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 , vol. 9 , 745637 . https://doi.org/10.3389/fcell.2021.745637

Title: Thrombospondin-4 Is a Soluble Dermal Inflammatory Signal That Selectively Promotes Fibroblast Migration and Keratinocyte Proliferation for Skin Regeneration and Wound Healing
Author: Klaas, Mariliis; Mäemets-Allas, Kristina; Heinmäe, Elizabeth; Lagus, Heli; Cardenas-Leon, Claudia Griselda; Arak, Terje; Eller, Mart; Kingo, Külli; Kankuri, Esko; Jaks, Viljar
Contributor organization: HUS Musculoskeletal and Plastic Surgery
Clinicum
Plastiikkakirurgian yksikkö
Esko Markus Kankuri / Principal Investigator
Medicum
Department of Pharmacology
Date: 2021-09-23
Language: eng
Number of pages: 17
Belongs to series: Frontiers in Cell and Developmental Biology
ISSN: 2296-634X
DOI: https://doi.org/10.3389/fcell.2021.745637
URI: http://hdl.handle.net/10138/337345
Abstract: 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 beta-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.
Subject: skin regeneration
wound healing
burns
thrombospondin-4
fibroblasts
psoriasis
BREAST-CANCER
EXPRESSION
INTEGRIN
ALPHA-2-BETA-1
MYOCARDIUM
REGULATORS
PROTEINS
TISSUE
BINDS
1182 Biochemistry, cell and molecular biology
1184 Genetics, developmental biology, physiology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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