Small Leucine-Rich Proteoglycans in Skin Wound Healing

Abstract

Healing of cutaneous wounds is a complex and well-coordinated process requiring cooperation among multiple cells from different lineages and delicately orchestrated signaling transduction of a diversity of growth factors, cytokines, and extracellular matrix (ECM) at the wound site. Most skin wound healing in adults is imperfect, characterized by scar formation which results in significant functional and psychological sequelae. Thus, the reconstruction of the damaged skin to its original state is of concern to doctors and scientists. Beyond the traditional treatments such as corticosteroid injection and radiation therapy, several growth factors or cytokines-based anti-scarring products are being or have been tested in clinical trials to optimize skin wound healing. Unfortunately, all have been unsatisfactory to date. Currently, accumulating evidence suggests that the ECM not only functions as the structural component of the tissue but also actively modulates signal transduction and regulates cellular behaviors, and thus, ECM should be considered as an alternative target for wound management pharmacotherapy. Of particular interest are small leucine-rich proteoglycans (SLRPs), a group of the ECM, which exist in a wide range of connecting tissues, including the skin. This manuscript summarizes the most current knowledge of SLRPs regarding their spatial-temporal expression in the skin, as well as lessons learned from the genetically modified animal models simulating human skin pathologies. In this review, particular focus is given on the diverse roles of SLRP in skin wound healing, such as anti-inflammation, pro-angiogenesis, pro-migration, pro-contraction, and orchestrate transforming growth factor (TGF)b signal transduction, since cumulative investigations have indicated their therapeutic potential on reducing scar formation in cutaneous wounds. By conducting this review, we intend to gain insight into the potential application of SLRPs in cutaneous wound healing management which may pave the way for the development of a new generation of pharmaceuticals to benefit the patients suffering from skin wounds and their sequelae.

Effects of the signal modulation on the response of human fibroblasts to in vitro stimulation with subthermal RF currents

“…Indeed, decorin exerts functions of alignment, stabilization and regulation of the diameter of collagen fibres, and acts as a bridge between various collagen types. Since it also performs as a signaling mediator of membrane receptors such as the epidermic growth factor receptor, decorin is considered a relevant biomarker in processes involved in skin aging or wound healing and regeneration (Hill et al 2018;Li et al 2007;Ma et al 2014;Pang et al 2020). In this context, the present results are suggestive that Hsp47, Hsp27 and decorin may take part of a pool of biomarkers whose electrically induced overexpression in fibroblasts could intervene in processes of cell migration, extracellular matrix contraction, collagenogenesis and fibrillogenesis, which are essential in tissue repair by CRET therapies.…”

Inflammation as an orchestrator of cutaneous scar formation: a review of the literature

“…Increasing fibromodulin levels via adenoviral overexpression or treating with recombinant fibromodulin has been shown to reduce scar formation in rabbit, mouse, and red Duroc pig wounds [ 153 – 156 ] . Based on these studies, a fibromodulin-based peptide has been developed and is currently being tested in clinical trials [ 157 ] .…”

Nonsurgical Management of Hypertrophic Scars: Evidence-Based Therapies, Standard Practices, and Emerging Methods: An Update

“…Of particular interest though is the recently elucidated diverse role of small leucine-rich proteoglycans (SLRPs), a group of extracellular matrix (ECM), in skin wound healing, such as anti-inflammation, pro-angiogenesis, pro-migration, procontraction, and orchestration of transforming growth factor (TGF-b) signal transduction. This may pave the way for the development of a new generation of pharmaceuticals with beneficial effects on wound healing and final scar formation [1].…”

“…The process is characterized by a complex and sensitive balance between activation and inhibition of inflammation and is well orchestrated and coordinated by signaling transduction of a diversity of growth factors, cytokines, and extracellular matrix (ECM) components [1,2]. Unfortunately most skin wound healing following trauma or surgery is imperfect and results in scar formation [1]. Hypertrophic scar (HTS) incidence is 4-16%, and approximately 35% of all surgical skin wounds result after 1 year in HTSs [3].…”

“…Hypertrophic scar (HTS) incidence is 4-16%, and approximately 35% of all surgical skin wounds result after 1 year in HTSs [3]. Though not life threatening, HTSs cause significant functional, cosmetic, and psychological sequelae [1] often overlooked, scars negatively impact to a great extent the individual's quality of life due to anxiety and depression, loss of self-esteem, stigmatization, and disruption of daily activities [4].…”