Inflammatory microenvironment and tumor necrosis factor alpha as modulators of periostin and CCN2 expression in human non-healing skin wounds and dermal fibroblasts

Elliott, Christopher G.; Forbes, Thomas L.; Leask, Andrew; Hamilton, David A.

doi:10.1016/j.matbio.2015.03.003

Cited by 30 publications

(30 citation statements)

References 45 publications

(62 reference statements)

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“…With respect to the regulation of galectin-3 expression in fibroblasts, we have shown that both TGF-b1 and TNF-a reduce galectin-3 expression in human dermal fibroblasts isolated from the wound edge of human chronic wounds, but not the noninvolved fibroblasts. This fits with trends that our group has reported previously (Elliott et al, 2015), suggesting that chronic wound fibroblasts, although not able to respond appropriately in vivo, respond strongly to certain stimuli in vitro. Because many fibrotic diseases correlate with high galectin-3 levels (Henderson et al, 2008;Jiang et al, 2012;MacKinnon et al, 2012) and TGF-b1 is a potent inducer of a fibrotic phenotype in fibroblasts (Desmoulière et al, 1993), reduced galectin-3 expression in response to TGF-b1 was unexpected.…”

Section: Discussionsupporting

confidence: 91%

Genetic Deletion of Galectin-3 Does Not Impair Full-Thickness Excisional Skin Healing

Walker

Elliott

Forbes

et al. 2016

Journal of Investigative Dermatology

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Galectin-3 has been linked to the regulation of several molecular processes essential during acute cutaneous wound healing, but a comprehensive study of the role of galectin-3 has yet to be performed. With known roles in macrophage polarization, myofibroblast differentiation, re-epithelialization, and angiogenesis, we hypothesized that genetic deletion of galectin-3 would significantly impair healing of excisional skin wounds in mice. In wild-type mice, galectin-3 expression correlated temporally with the inflammatory phase of healing. Conversely, genetic deletion of galectin-3 did not alter gross wound healing kinetics even though it resulted in delayed re-epithelialization. Wound composition was not altered up to 15 days after wounding in knockout mice, and isolated dermal fibroblast function in vitro was unchanged. We further explored, spatially, the expression of galectin-3 in human chronic wound tissue in relation to the immune cell infiltrate. We show a decreased mRNA and protein abundance in the wound edge tissue, whereas markers of neutrophils, M1 and M2 macrophages are expressed abundantly. Both transforming growth factor-β1 and tumor necrosis factor-α decrease galectin-3 mRNA abundance in chronic wound edge dermal fibroblasts in vitro, providing a potential mechanism for this decreased expression in chronic wounds.

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Section: Discussionsupporting

confidence: 91%

Genetic Deletion of Galectin-3 Does Not Impair Full-Thickness Excisional Skin Healing

Walker

Elliott

Forbes

et al. 2016

Journal of Investigative Dermatology

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“…To determine whether altered kinetics of inflammatory cells recruitment resulted from the chemokine and cytokine expression, the chemokine Ccl2 and cytokine TNF-␣, which are chemoattractants for neutrophils and macrophages (Elliott, Forbes, Leask, & Hamilton, 2015;Sindrilaru et al, 2011;Tymen et al, 2013), were measured by Western blot in wound tissue on days 1, 2 and 6 after wounding. The levels of Ccl2 (Fig.…”

Section: Inflammatory Cell Recruitment Into the Wound Sitesmentioning

confidence: 99%

Nano-porous nitrocellulose liquid bandage modulates cell and cytokine response and accelerates cutaneous wound healing in a mouse model

Zhang

et al. 2016

Carbohydrate Polymers

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“…Galectin-3, posited to possess certain properties of a matricellular protein through its localization in the extracellular matrix (ECM) (Ochieng et al 2002;Melo et al 2011), is also established to have several intracellular functions (Funasaka et al 2014;Honig et al 2015;Fritsch et al 2016). Galectin-3 is implicated in several inflammatory and immunomodulatory processes, making it an ideal candidate for treatment of chronic skin wounds, where the lesions remain in a toxic pro-inflammatory state (Elliott et al 2015). Galectin-3 has been shown to influence monocyte and macrophage migration (Sano et al 2000), increase clearance of neutrophils (Karlsson et al 2009), and regulate alternative macrophage polarization (MacKinnon et al 2008), all processes that can contribute to modulating the inflammatory r e s p o n s e .…”

Section: Introductionmentioning

confidence: 99%

Galectin-3 regulation of wound healing and fibrotic processes: insights for chronic skin wound therapeutics

McLeod

Walker

Hamilton

2018

J. Cell Commun. Signal.

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A member of the lectin family, galectin-3 is a 250 amino-acid protein that contains a C-terminus carbohydrate recognition domain (CRD) that recognizes β-galactosides. Considered to have certain common properties associated with matricellular proteins, galectin-3 is expressed in the dermis and epidermis in healthy skin and is upregulated in skin healing, peaking at day 1 post wounding in mice. Galectin-3 has been implicated in several processes central to the wound healing response, specifically in the regulation of inflammation, macrophage polarization, angiogenesis, fibroblast to myofibroblast transition and re-epithelialization. However, it appears that many of the effects of Galectin-3 are highly tissue specific and context dependent. Genetic deletion of galectin-3 shows different effects in skin compared to lung, heart, and kidney remodeling. In this review, we will compare galectin-3 functions in these tissues. Furthermore, we will discuss, based on its identified regulation of cell processes, whether in an exogenous form, galectin-3 could represent a novel therapeutic for impaired skin healing.

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Inflammatory microenvironment and tumor necrosis factor alpha as modulators of periostin and CCN2 expression in human non-healing skin wounds and dermal fibroblasts

Cited by 30 publications

References 45 publications

Genetic Deletion of Galectin-3 Does Not Impair Full-Thickness Excisional Skin Healing

Genetic Deletion of Galectin-3 Does Not Impair Full-Thickness Excisional Skin Healing

Nano-porous nitrocellulose liquid bandage modulates cell and cytokine response and accelerates cutaneous wound healing in a mouse model

Galectin-3 regulation of wound healing and fibrotic processes: insights for chronic skin wound therapeutics

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