Impact of ECM proteins in cancer and wound-healing microenvironments

Cell slides from a microscope
Force sensing mechanism bestowed by sAgrin

Our long-term goal is to investigate the role of Agrin as a bio-additive or its usage within biological scaffolds that may aid tissue healing and promote regeneration.

An orchestrated wound healing program drives skin repair via collective epidermal cell proliferation and migration. However, the molecular determinants of the tissue microenvironment supporting wound healing remain poorly understood.

On this front, our recent studies revealed that timely induction of Agrin or exogenous supplementation of recombinant Agrin accelerated the healing of injured skin tissues by improving angiogenesis, ECM deposition, and mechanical parameters:

We discovered that proteoglycan Agrin is enriched within the early wound-microenvironment and is indispensable for efficient healing. Agrin enhances the mechanoperception of keratinocytes and promotes efficient wound-induced migration via inducing matrix metalloproteinase-12 (MMP12).

Figure from a scientific research study
sAgrin therapy accelerates skin wound healing in mice (upper panel) and restoration of ECM (collagen network) by sAgrin therapy (lower panel).

Interestingly, we devised a recombinant Agrin (sAgrin) fragment as a bio-additive material that assimilates optimal mechanobiological and pro-angiogenic parameters by engaging MMP12 in accelerated wound healing.

Further studies are in progress to understand the mechanism of sAgrin to accelerate wound healing and devise appropriate biomaterials to incorporate sAgrin.

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Department of Pharmacology & Therapeutics
Roswell Park Comprehensive Cancer Center
Elm and Carlton Streets
Buffalo, NY 14263