PDGF signaling pathway in hepatic fibrosis pathogenesis and therapeutics

Abstract

The platelet-derived growth factor (PDFG) signaling pathway exerts persistent activation in response to a variety of stimuli and facilitates the progression of hepatic fibrosis. Since this pathway modulates a broad spectrum of cellular processes, including cell growth, differentiation, inflammation and carcinogenesis, it has emerged as a therapeutic target for hepatic fibrosis and liver-associated disorders. The present review exhibits the current knowledge of the role of the PDGF signaling pathway and its pathological profiles in hepatic fibrosis, and assesses the potential of inhibitors which have been investigated in the experimental hepatic fibrosis model, in addition to the clinical challenges associated with these inhibitors.

Freeze-Dried Platelet-Rich Plasma Induces Osteoblast Proliferation via Platelet-Derived Growth Factor Receptor-Mediated Signal Transduction

“…ERKs play a central role in cell survival and mitogenic signaling, while the JNK and p38 MAP kinases induce various stress responses, including apoptosis, inflammation, and differentiation [29]. Various studies have reported that ERK acts downstream of the PDGF pathway and regulates cell proliferation [30]. Both fresh-PRP and FD-PRP activated PDGFR and its downstream target ERK in osteoblasts, indicating that PDGF concentration in PRP is sufficient to induce the proliferation of osteoblasts via the PDGFR-mediated ERK signaling pathway (Figs.…”

Rebaudioside A administration prevents experimental liver fibrosis: an in vivo and in vitro study of the mechanisms of action involved

“…In this scenario, it is reasonable to propose that Reb A, similar to stevioside, may protect the liver by exerting the immunomodulatory and antifibrogenic effects, downregulating the NF‐κB pathway and modulating the MAPK pathway. Another pathway, the PDGF pathway, modulates a broad spectrum of cellular responses, such as cell growth, differentiation, inflammation and carcinogenesis, actively participating in HSC activation during the early stage of liver injury and exacerbating the production of ECM (Ying et al, ). Therefore, modulation of the PDGFR by Reb A could explain, at least in part, the beneficial effects of Reb A observed in cocultured cells and in rat‐induced chronic liver injury.…”

Cytokine profile in children with food allergy following liver transplantation

“…Reduced levels of the pro‐inflammatory MIP‐1a also indicate that Th1 inflammation is affected. PDGF is a growth factor highly involved in the development of liver fibrosis and is associated with chronic inflammation . Chemokines (as RANTES or chemokine ligand 5) are relevant in allergy because of their role in regulating leukocyte recruitment, but also for cellular activation, inflammatory mediator release, promotion of Th2 inflammatory responses, and regulation of IgE .…”

“…PDGF is a growth factor highly involved in the development of liver fibrosis and is associated with chronic inflammation. 30,31 Chemokines (as RANTES or chemokine ligand 5) are relevant in allergy because of their role in regulating leukocyte recruitment, but also for cellular activation, inflammatory mediator release, promotion of Th2 inflammatory responses, and regulation of IgE. 32 RANTES has been linked to recruitment of Th2 cells, 33 and TNFα is thought to play a major role in the pathogenesis of allergy and inflammatory diseases as it is produced at an early stage of allergen sensitization and continues to promote the inflammation cascade throughout the allergy development.…”