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      Primary Ciliary Signaling in the Skin—Contribution to Wound Healing and Scarring

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          Abstract

          Primary cilia (PC) are solitary, post-mitotic, microtubule-based, and membrane-covered protrusions that are found on almost every mammalian cell. PC are specialized cellular sensory organelles that transmit environmental information to the cell. Signaling through PC is involved in the regulation of a variety of cellular processes, including proliferation, differentiation, and migration. Conversely, defective, or abnormal PC signaling can contribute to the development of various pathological conditions. Our knowledge of the role of PC in organ development and function is largely based on ciliopathies, a family of genetic disorders with mutations affecting the structure and function of PC. In this review, we focus on the role of PC in their major signaling pathways active in skin cells, and their contribution to wound healing and scarring. To provide comprehensive insights into the current understanding of PC functions, we have collected data available in the literature, including evidence across cell types, tissues, and animal species. We conclude that PC are underappreciated subcellular organelles that significantly contribute to both physiological and pathological processes of the skin development and wound healing. Thus, PC assembly and disassembly and PC signaling may serve as attractive targets for antifibrotic and antiscarring therapies.

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          Wnt/β-catenin signaling and disease.

          The WNT signal transduction cascade controls myriad biological phenomena throughout development and adult life of all animals. In parallel, aberrant Wnt signaling underlies a wide range of pathologies in humans. In this Review, we provide an update of the core Wnt/β-catenin signaling pathway, discuss how its various components contribute to disease, and pose outstanding questions to be addressed in the future. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Cell signaling by receptor tyrosine kinases.

            Recent structural studies of receptor tyrosine kinases (RTKs) have revealed unexpected diversity in the mechanisms of their activation by growth factor ligands. Strategies for inducing dimerization by ligand binding are surprisingly diverse, as are mechanisms that couple this event to activation of the intracellular tyrosine kinase domains. As our understanding of these details becomes increasingly sophisticated, it provides an important context for therapeutically countering the effects of pathogenic RTK mutations in cancer and other diseases. Much remains to be learned, however, about the complex signaling networks downstream from RTKs and how alterations in these networks are translated into cellular responses.
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              Mechanisms of fibrosis: therapeutic translation for fibrotic disease.

              Fibrosis is a pathological feature of most chronic inflammatory diseases. Fibrosis, or scarring, is defined by the accumulation of excess extracellular matrix components. If highly progressive, the fibrotic process eventually leads to organ malfunction and death. Fibrosis affects nearly every tissue in the body. Here we discuss how key components of the innate and adaptive immune response contribute to the pathogenesis of fibrosis. We also describe how cell-intrinsic changes in important structural cells can perpetuate the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix-producing myofibroblasts. Finally, we highlight some of the key mechanisms and pathways of fibrosis that are being targeted as potential therapies for a variety of important human diseases.
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                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                13 November 2020
                2020
                : 8
                : 578384
                Affiliations
                [1] 1Faculty of Medicine, Department of Pharmacology, University of Helsinki , Helsinki, Finland
                [2] 2Institute of Molecular and Cell Biology, University of Tartu , Tartu, Estonia
                [3] 3Dermatology Clinic, Tartu University Hospital , Tartu, Estonia
                [4] 4Department of Plastic Surgery and Wound Healing Centre, Helsinki University Hospital, University of Helsinki , Helsinki, Finland
                [5] 5Helsinki University Hospital, University of Helsinki , Helsinki, Finland
                [6] 6Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School , Tokyo, Japan
                Author notes

                Edited by: Satoshi Takagi, Fukuoka University, Japan

                Reviewed by: Dorothy Supp, University of Cincinnati, United States; Hongmin Qin, Texas A&M University, United States

                *Correspondence: Esko Kankuri esko.kankuri@ 123456helsinki.fi

                This article was submitted to Cell Growth and Division, a section of the journal Frontiers in Cell and Developmental Biology

                Article
                10.3389/fcell.2020.578384
                7691485
                33282860
                a5bc56cd-cd12-4c0b-9c89-6d74458ba7c5
                Copyright © 2020 Hosio, Jaks, Lagus, Vuola, Ogawa and Kankuri.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 June 2020
                : 08 October 2020
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 326, Pages: 22, Words: 20328
                Funding
                Funded by: Estonian Research Competency Council 10.13039/501100005189
                Categories
                Cell and Developmental Biology
                Review

                primary cilia,cell signaling,scar formation,wound healing,inflammation,fibroblast,myofibroblast

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