Stelic Institute & Co. focuses on the 2nd hit “remodeling phase” of fibrosis. Since fibrosis involves multi-factorial cascades including profibrotic factors, MMP-TIMP balance, EMT-MET balance, ECM balance and repair-remodeling balance, it is a challenge to stop fibrosis by regulating a single mediator alone. In addition, removal of collagen might affect destruction of normal tissue structure and TGF-blockade might inhibit regulatory T cells leading to severe inflammation. In contrast, the G family acts as ‘fine tuner’ of multi-factorial cascades.
The G-family is up-regulated in inflammatory cells such as mast cells, macrophages and fibroblasts in response to inflammatory stimuli. G family-derived glycoprotein provides scaffolds of fibroblasts to be activated and accumulated. This leads to multi-factorial cascades; up-regulation of profibrotic factors like TGF-β, activation of TIMP over MMP, promotion of EMT, increased deposition of ECMs and impaired tissue integrity (Below figure). Blocking specific a G family alone depletes the fibroblast-creating niche leading to bulk normalization of multi-factorial cascades.
G family is a fine tuner that controls multiple factors at sites of fibrosis. TGF: transforming growth factor, CTGF: connecting tissue growth factor, CCL: CC chemokine ligand, Ang: Angiotensin, PDGF: platelet derived growth factor, MMP: metalloproteinase, TIPM: tissue inhibitor of metalloproteinase, BMP: bone morphogenetic protein, EMT: epithelial mesenchymal transition, MET: mesenchymal epithelial transition, ECM: extracellular matrix, GP: glycoprotein, PG: proteoglycan.
