Biomolecules that impact phenotypic transitions in fibroblasts and macrophages

Forsmark, Kiva
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Macrophages and fibroblasts are intricately involved in many biological responses. The foreign body response (FBR) is orchestrated by macrophages, wherein the phenotypes of these macrophages exist plastically along a spectrum from M1, proinflammatory macrophages to M2a, anti-inflammatory, pro-wound healing macrophages, and M2c, regulatory macrophages. The timely progression of macrophages through these phenotypic changes is necessary for the resolution of this response. Interplay between M2a macrophages, myofibroblasts and M2c macrophages is responsible for the eventual resolution of this response. Following, transforming growth factor-β (TGF-β) activation, fibroblasts differentiate into myofibroblasts; these cells will secrete and contract extracellular matrix (ECM) components into a fibrous capsule. Herein, a library of modified poly-L-arginine (PLR) was used to influence the fibroblast to myofibroblast transition, and it was found that small variances in chemical modification allow for or impede this process. This excessive ECM deposition is also characteristic of some cancers that undergo what is known as a desmoplastic response. Desmoplasia is most often cancer promoting. Like the FBR, this response involves M1, M2a, and M2c macrophages and myofibroblasts. Increased levels and sulfation patterns of chondroitin sulfates (CS) and their associated proteoglycans are associated with this response. Increased arginase activity, increased iNOS activity, and morphological changes, indicating phenotypic changes in macrophages, were seen when CS-A, CS-B, CS-C, and CS-E were cultured with RAW 264.7 macrophages of five different phenotypes.

Chemical Engineering, Cancer, Chondroitin sulfate, Foreign body response, Macrophages, Myofibroblasts, Poly-L-arginine