The complex dialogue between (myo)fibroblasts and the extracellular matrix during skin repair processes and ageing

Védrenne, Nicolas; Coulomb, Bernard; Danigo, Aurore; Bonté, Frédéric; Desmoulière, Alexis

doi:10.1016/j.patbio.2011.10.002

Cited by 73 publications

(49 citation statements)

References 103 publications

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“…80 The main function of fibroblasts is to maintain the physical integrity of connective tissue by producing and remodelling the ECM. 81 Integrin receptors on the cell surface of fibroblasts provide contact with the surrounding ECM. 82 Of the two major fibronectin integrin receptors, aVb3 and a5b1, the latter is the primary receptor for soluble fibronectin and has a key role in assembling fibronectin into fibrils, though aVb3 can assemble fibrils in cells that lack a5b1.…”

Section: (Myo)fibroblastsmentioning

confidence: 99%

Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

Xue

Jackson

2015

Advances in Wound Care

992

866

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Significance: When a cutaneous injury occurs, the wound heals via a dynamic series of physiological events, including coagulation, granulation tissue formation, re-epithelialization, and extracellular matrix (ECM) remodeling. The final stage can take many months, yet the new ECM forms a scar that never achieves the flexibility or strength of the original tissue. In certain circumstances, the normal scar is replaced by pathological fibrotic tissue, which results in hypertrophic or keloid scars. These scars cause significant morbidity through physical dysfunction and psychological stress. Recent Advances and Critical Issues: The cutaneous ECM comprises a complex assortment of proteins that was traditionally thought to simply provide structural integrity and scaffolding characteristics. However, recent findings show that the ECM has multiple functions, including, storage and delivery of growth factors and cytokines, tissue repair and various physiological functions. Abnormal ECM reconstruction during wound healing contributes to the formation of hypertrophic and keloid scars. Whereas adult wounds heal with scarring, the developing foetus has the ability to heal wounds in a scarless fashion by regenerating skin and restoring the normal ECM architecture, strength, and function. Recent studies show that the lack of inflammation in fetal wounds contributes to this perfect healing. Future Directions: Better understanding of the exact roles of ECM components in scarring will allow us to produce therapeutic agents to prevent hypertrophic and keloid scars. This review will focus on the components of the ECM and their role in both physiological and pathological (hypertrophic and keloid) cutaneous scar formation. SCOPE AND SIGNIFICANCEThis article reviews the extracellular matrix (ECM) and its remodeling during normal cutaneous wound healing and scar formation, and the differential response of the components of the ECM and their role in pathological (hypertrophic and keloid) cutaneous scar formation. This review focuses on the major players involved in the irregular ECM production as being; fibroblasts and their immature counterparts, myofibroblasts; collagens; transforming growth factor (TGF)-b, which controls the production of collagens; proteoglycans and matrix metalloproteinases (MMPs). We also highlight the complexity of interactions occurring in the ECM of skin during (ab) normal scar formation. TRANSLATIONAL RELEVANCEAbnormal ECM, particularly abnormal collagen remodeling and reorganization, accounts for one of the most important contributing factors to abnormal scarring. Identification of the exact ECM molecules involved in causing abnormal scarring is likely to provide a future treatment target. This may be achieved by promoting the correct balance in collagen ratios or by directly targeting the production of collagen. Overall, a better understanding of the exact roles of ECM components in scarring will help us to produce therapeutic agents to prevent and treat hypertrophic and keloid scars. CLINICAL RELEVANCEThere ...

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Section: (Myo)fibroblastsmentioning

confidence: 99%

Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

Xue

Jackson

2015

Advances in Wound Care

992

866

View full text Add to dashboard Cite

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“…If translated to humans, these effects may lead to improvements in skin function in the elderly. Studies have shown a close relationship between the ECM microenvironment (including mechanical properties of young relative to aged collagen) and synthesis of molecules that regulate cell-ECM attachment, repair, and turnover by resident dermal fibroblasts (18,24,35,36). Moreover, degraded ECM is central to facilitating tumor metastasis (37,38), suggesting that preventing or limiting local GC activation may also reduce skin cancer risk.…”

Section: Figurementioning

confidence: 99%

11β-Hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects

Tiganescu

Tahrani²,

Morgan³

et al. 2013

J. Clin. Invest.

115

120

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Glucocorticoid (GC) excess adversely affects skin integrity, inducing thinning and impaired wound healing. Aged skin, particularly that which has been photo-exposed, shares a similar phenotype. Previously, we demonstrated age-induced expression of the GC-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in cultured human dermal fibroblasts (HDFs). Here, we determined 11β-HSD1 levels in human skin biopsies from young and older volunteers and examined the aged 11β-HSD1 KO mouse skin phenotype. 11β-HSD1 activity was elevated in aged human and mouse skin and in PE compared with donor-matched photo-protected human biopsies. Age-induced dermal atrophy with deranged collagen structural organization was prevented in 11β-HSD1 KO mice, which also exhibited increased collagen density. We found that treatment of HDFs with physiological concentrations of cortisol inhibited rate-limiting steps in collagen biosynthesis and processing. Furthermore, topical 11β-HSD1 inhibitor treatment accelerated healing of full-thickness mouse dorsal wounds, with improved healing also observed in aged 11β-HSD1 KO mice. These findings suggest that elevated 11β-HSD1 activity in aging skin leads to increased local GC generation, which may account for adverse changes occurring in the elderly, and 11β-HSD1 inhibitors may be useful in the treatment of age-associated impairments in dermal integrity and wound healing.

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“…This response involves the action of growth factors such as transforming growth factor beta (TGF-b), which promotes the appearance of specialized fibroblasts termed myofibroblasts, which are characterized by the expression of the highly contractile protein a-smooth muscle actin (a-SMA), which appears in the cell as cables connected to the ECM through cell surface structures called focal adhesions (FAs). 1 FAs contain clusters of integrins, which are the cell surface ECM receptors. Myofibroblasts are not only essential for executing connective tissue repair but they also are responsible for scarring and fibrotic disease.…”

Section: Scopementioning

confidence: 99%

“…Myofibroblasts are not only essential for executing connective tissue repair but they also are responsible for scarring and fibrotic disease. 1 It is now appreciated that substantial crosstalk exists between growth factor and adhesive signaling pathways. In particular, adhesion-mediated activation of focal adhesion kinase (FAK), which is recruited to FA postintegrin clustering, appears to be essential for myofibroblast differentiation and activity.…”

Section: Scopementioning

confidence: 99%

Focal Adhesion Kinase: A Key Mediator of Transforming Growth Factor Beta Signaling in Fibroblasts

Leask

2013

Advances in Wound Care

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The complex dialogue between (myo)fibroblasts and the extracellular matrix during skin repair processes and ageing

Cited by 73 publications

References 103 publications

Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

11β-Hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects

Focal Adhesion Kinase: A Key Mediator of Transforming Growth Factor Beta Signaling in Fibroblasts

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