Notch Signaling in Embryology and Cancer by Jörg Reichrath & Sandra Reichrath

Author:Jörg Reichrath & Sandra Reichrath
Language: eng
Format: epub
ISBN: 9783030364229
Publisher: Springer International Publishing

Role of Gremlin-1 in Fibrosis and EMT

Fibrosis is characterized by an excessive accumulation of extracellular matrix proteins (ECM), such as collagens and fibronectin, which are overexpressed by some cells, mainly activated myofibroblasts. This fibrotic response is naturally produced by the organism in physiological processes. However, when the fibrotic response is exacerbated, it could induce tissue damage and function failure (Lee and Kalluri 2010). Our group discovered that Gremlin-1 increased the expression of stimulated profibrotic factors and the production of ECM components including CTGF, fibronectin, collagen and PAI-1 in murine renal fibroblasts in vitro (Rodrigues-Diez et al. 2013) (Fig. 6.3). Other in vitro studies have found that Gremlin-1 can regulate ECM production in different cell types (Mezzano et al. 2018). However, the direct effect of Gremlin-1 in fibrotic process has not been completely demonstrated.

Fig. 6.3Gremlin-mediated partial EMT and fibroblasts activation in the kidney. Gremlin-1 is known to produce partial EMT in epithelial cells, as well as activating local fibroblasts, thus producing an increase in extracellular matrix components (ECM) and subsequent tubulointerstitial fibrosis

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