The hard problem: Mechanotransduction perpetuates the myofibroblast phenotype in scleroderma fibrosis

Leask, Andrew

doi:10.1111/wrr.12889

Cited by 17 publications

(8 citation statements)

References 86 publications

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“…For example, the excessive fibroblast activity, often occurring in large burns and severe injuries, results in hypertrophic scarring and keloid formation (i.e., dysfunctional and disfiguring scar tissue) ( Hinz, 2016 ; Arif et al, 2021 ). The persistence of myofibroblast activity can also be caused by altered signaling pathways ( Leask, 2021 ), apoptosis failure ( Hinz and Lagares, 2020 ), and excessive mechanical stress, as in the case of high strains at the wound edges ( Wong et al, 2011a ) or ECM stiffness ( Sawant et al, 2021 ).…”

Section: Fibroblast Dysfunction In Wound Healingmentioning

confidence: 99%

Role of fibroblasts in wound healing and tissue remodeling on Earth and in space

Cialdai

Risaliti²,

Monici³

2022

Front. Bioeng. Biotechnol.

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Wound healing (WH) and the role fibroblasts play in the process, as well as healing impairment and fibroblast dysfunction, have been thoroughly reviewed by other authors. We treat these topics briefly, with the only aim of contextualizing the true focus of this review, namely, the microgravity-induced changes in fibroblast functions involved in WH. Microgravity is a condition typical of spaceflight. Studying its possible effects on fibroblasts and WH is useful not only for the safety of astronauts who will face future interplanetary space missions, but also to help improve the management of WH impairment on Earth. The interesting similarity between microgravity-induced alterations of fibroblast behavior and fibroblast dysfunction in WH impairment on Earth is highlighted. The possibility of using microgravity-exposed fibroblasts and WH in space as models of healing impairment on Earth is suggested. The gaps in knowledge on fibroblast functions in WH are analyzed. The contribution that studies on fibroblast behavior in weightlessness can make to fill these gaps and, consequently, improve therapeutic strategies is considered.

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Section: Fibroblast Dysfunction In Wound Healingmentioning

confidence: 99%

Role of fibroblasts in wound healing and tissue remodeling on Earth and in space

Cialdai

Risaliti²,

Monici³

2022

Front. Bioeng. Biotechnol.

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“…[14][15][16][17] Fibrosis and scarring ensue when normal skin repair persists, for instance when myofibroblast fail to die 18,19 or when danger signals and inflammation become chronic like in systemic sclerosis. 20,21 Functional skin becomes then replaced by dysfunctional and disfiguring scar tissue. In other organs, fibrous ECM can confuse and stress fibroblasts and other cells to the point of organ dysfunction or failure, like in lung fibrosis, 22,23 palmar fascia in Dupuytren disease 24,25 , glaucoma, 26 and heart fibrosis.…”

Section: Introductionmentioning

confidence: 99%

A story of fibers and stress: Matrix‐embedded signals for fibroblast activation in the skin

Sawant

Hinz

Schönborn

et al. 2021

Wound Repair Regeneration

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Our skin is continuously exposed to mechanical challenge, including shear, stretch, and compression. The extracellular matrix of the dermis is perfectly suited to resist these challenges and maintain integrity of normal skin even upon large strains. Fibroblasts are the key cells that interpret mechanical and chemical cues in their environment to turnover matrix and maintain homeostasis in the skin of healthy adults. Upon tissue injury, fibroblasts and an exclusive selection of other cells become activated into myofibroblasts with the task to restore skin integrity by forming structurally imperfect but mechanically stable scar tissue. Failure of myofibroblasts to terminate their actions after successful repair or upon chronic inflammation results in dysregulated myofibroblast activities which can lead to hypertrophic scarring and/or skin fibrosis. After providing an overview on the major fibrillar matrix components in normal skin, we will interrogate the various origins of fibroblasts and myofibroblasts in the skin. We then examine the role of the matrix as signaling hub and how fibroblasts respond to mechanical matrix cues to restore order in the confusing environment of a healing wound.

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“…The proin ammatory transition is gated by retinoic acid Progression of wound healing phases is associated with dynamic biochemical and biomechanical signals such as TGFβ and Wnt 48 , cytokines such as Interleukins and Tumor necrosis factor 49 , cell-cell interactions [50][51] , and extracellular matrix mechano-transduction 4,52 .…”

Section: Sequential Checkpoints Control Cd201 + Progenitor Differenti...mentioning

confidence: 99%

CD201+ fascia progenitors choreograph injury repair

Rinkevich

Correa-Gallegos

et al. 2022

Preprint

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Optimal tissue recovery and organismal survival1 are achieved by tight spatiotemporal tuning of tissue inflammation, contraction and scar-formation. Here, we discover a multipotent fibroblast progenitor marked by CD201 expression in the fascia, the deepest connective tissue layer of the skin. Using murine skin injury models, single-cell transcriptomics, and genetic lineage tracing and ablation models, we demonstrate that CD201+ progenitors pace wound healing by generating multiple specialized cell types from proinflammatory fibroblasts to myofibroblasts in a spatiotemporally tuned sequence. We identify retinoic acid and hypoxia signaling as differentiation checkpoints that control the graduated entry of fascia progenitor into the proinflammatory and myofibroblast states. Modulating their differentiation, with retinoic acid and hypoxia-inducible factor 1-alpha, or genetically ablating this cellular lineage, impaired the graduated appearances of specialized fibroblasts and chronically delayed wound healing. The discovery of fascia progenitors, their microenvironment, and the signaling pathways that control the graduated transitions thereof provides a new roadmap to understand and clinically treat impaired wound healing.

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The hard problem: Mechanotransduction perpetuates the myofibroblast phenotype in scleroderma fibrosis

Cited by 17 publications

References 86 publications

Role of fibroblasts in wound healing and tissue remodeling on Earth and in space

Role of fibroblasts in wound healing and tissue remodeling on Earth and in space

A story of fibers and stress: Matrix‐embedded signals for fibroblast activation in the skin

CD201+ fascia progenitors choreograph injury repair

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