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

Abstract

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.

Galectin-3 Induces a Pro-degradative/inflammatory Gene Signature in Human Chondrocytes, Teaming Up with Galectin-1 in Osteoarthritis Pathogenesis

“…Such a responsiveness is known for other cell types, e.g. chronic wound edge (but not non-involved) fibroblasts, in which TNF-α even reduces LGALS3 expression (p = 0.032)40. In the tested OA chondrocytes, it was also not subject to auto-regulation, despite the presence of two putative binding sites for NF-κB in the promoter of the human gene for Gal-341.…”

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

“…Based on the defined role of galectin-3 on regulation of inflammatory processes, this data was surprising, as it suggests that galectin-3 is not required for inflammatory cell recruitment in this particular pathology. The inflammatory cell profile in chronic wounds is associated with variable macrophage phenotypes and neutrophil infiltration, which is dependent on the individual wound examined (Walker et al 2016).…”

“…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 . Wi t h d e m o n s tr a te d r e g u l a ti o n o f r eepithelialization (Cao et al 2002;Saravanan et al 2009;Panjwani 2014) and contrasting data on its modulation of myofibroblast differentiation (Okamura et al 2011;Mackinnon et al 2012;Walker et al 2016), it could be hypothesized that the use of galectin-3 would provide an effective strategy in promoting healing by stimulating the proliferative phase of healing. The focus of this review is to discuss the role of galectin-3 in various models of wound healing and fibrosis, and whether galectin-3 could potentially be utilized for resolution of impaired skin healing.…”

Transcriptomic responses to wounding: meta-analysis of gene expression microarray data

“…The Lgals3 knockout was shown to reduce the re-epithelisation rate in murine skin, but the overall wound healing rate remained largely unaffected. Nevertheless, it might be an important factor in chronic wound development [ 18 ]. However, there are animal models where positive impacts of single gene deletion have been shown.…”