Enhanced secretion of TIMP-1 by human hypertrophic scar keratinocytes could contribute to fibrosis

Simon, Franck; Bergeron, Danielle; Larochelle, Sébastien; Lopez-Vallé, Carlos A.; Genest, Hervé; Armour, Alexis D.; Moulin, Véronique J.

doi:10.1016/j.burns.2011.09.001

Cited by 71 publications

(53 citation statements)

References 36 publications

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“…130,131 There is relatively strong expression of TIMP-1 in hypertrophic scar biopsies in contrast to very low levels of TIMP-1 in normal skin. 92 Less synthesis of molecules that promote matrix breakdown (e.g., MMPs) may also explain the lack of scar regression seen in keloids. 75 However, there have been reports that the ECM of keloids shows elevated levels of MMPs (Table 4).…”

Section: Matrix Metalloproteinasesmentioning

confidence: 99%

“…Although TGF-b1 induces the expression of MMP-2, -9, and -13 in fibroblasts, it actually reduces collagen degradation by inhibiting the expression of MMP-1 and increasing the production of TIMP-1. 92,93 There are three isoforms of TGF-a-TGF-b1 and TGF-b2 have the profibrotic properties whereas TGF-b3 is antifibrotic. 93 TGF-b1 signalling activates SMAD2 and SMAD3, which use SMAD4 for translocation to the nucleus, whereas TGF-b3 stimulates Smad7.…”

Section: (Myo)fibroblastsmentioning

confidence: 99%

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

Xue

Jackson

2015

Advances in Wound Care

1,090

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: Matrix Metalloproteinasesmentioning

confidence: 99%

Section: (Myo)fibroblastsmentioning

confidence: 99%

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

Xue

Jackson

2015

Advances in Wound Care

1,090

866

View full text Add to dashboard Cite

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“…Scarless wound healing has been thought to be mediated by human dermal fibroblasts and the epidermis is thought to play an insignificant role [1,2]. However, several previous studies have demonstrated that normal KCs secrete factors known to modulate fibroblast secretion of collagen and MMPs [18]. Furthermore, a recent study has suggested that pathological KCs can contribute to scar formation, enhancing dermal thickness in comparison to normal KCs due to enhanced collagen secretion and decreased MMP-1 secretion [19].…”

Section: Discussionmentioning

confidence: 97%

Phenotypic and functional modulation of 20–30 year old dermal fibroblasts by mid- and late-gestational keratinocytes in vitro

Wang¹,

Liu²,

Zhang³

et al. 2015

Burns

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“…22 Decreased levels of MMP-2, MMP-9, and increased levels of TIMP-1 were found in patients with hypertrophic scars. 14,23 Another study showed that MMP-1, MMP-2, and MMP-9 are up-regulated by the interaction between fibroblasts and keratinocytes, indicating the role of keratinocytes as additional regulators of ECM formation and degradation. 24,25 Keratinocyte derived stratifin was shown to stimulate MMP-1 expression in dermal fibroblasts through c-fos and p38 mitogen-activated protein kinase (MAPK) pathway 26 ; however, this simulation was reversed by insulin.…”

Section: Scar Biology Research Overviewmentioning

confidence: 99%

Scarless Tissue Regeneration

Golberg¹

2017

Frontiers in Nanobiomedical Research

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Wounds and wound healing are parts of every organism's life. What is a wound, how does it heal and what can we do to speed the healing, but decrease scarring? All these fundamental questions occupy the minds of people through all known history. Wound healing is an extremely complex phenomenon, which involves both the organism and its environment. Moreover, chemical, biological, mechanical and electrical forces drive this phenomenon. This chapter attempts to combine various aspects of wound healing phenomena with an emphasis on scarless regeneration. The system approach to wound healing is needed to develop new therapies. This chapter starts with the general overview on what is a wound from the system perspective. Then it describes the highlevel events that take place during normal and abnormal wound healing. Next, it gives a historic perceptive on the history of wound healing in humans. Then it describes the fundamentals of scar biology, going to the details of known biochemical and cellular events involved in the process of scar formation. It then deals with the mechanical and electrical events that affect wound healing process. Next, complex events such as inflammation and wound-bacteria interaction are discussed, followed by descriptions of the in vitro and in vivo models of scarless wound healing. This chapter concludes with open questions and future perspectives of scarless wound healing.

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Enhanced secretion of TIMP-1 by human hypertrophic scar keratinocytes could contribute to fibrosis

Cited by 71 publications

References 36 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

Phenotypic and functional modulation of 20–30 year old dermal fibroblasts by mid- and late-gestational keratinocytes in vitro

Scarless Tissue Regeneration

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