FSP1 promotes the biofunctions of adventitial fibroblast through the crosstalk among RAGE, JAK2/STAT3 and Wnt3a/β‐catenin signalling pathways

Abstract

Emerging evidence indicates that fibroblast‐specific protein 1 (FSP1) provides vital effects in cell biofunctions. However, whether FSP1 influences the adventitial fibroblast (AF) and vascular remodelling remains unclear. Therefore, we investigated the potential role and action mechanism of FSP1‐mediated AF bioactivity. AFs were cultured and stimulated with FSP1 and siRNA‐FSP1 in vitro. Viability assays demonstrated that siRNA‐FSP1 counteracted AFs proliferative, migratory and adherent abilities enhanced with FSP1. Flow cytometry revealed that FSP1 increased AFs number in S phase and decreased cellular apoptosis. Contrarily, siRNA‐FSP1 displayed the contrary results. RT‐PCR, Western blotting and immunocytochemistry showed that FSP1 synchronously up‐regulated the expression of molecules in RAGE, JAK2/STAT3 and Wnt3a/β‐catenin pathways and induced a proinflammatory cytokine profile characterized by high levels of MCP‐1, ICAM‐1 and VCAM‐1. Conversely, FSP1 knockdown reduced the expression of these molecules and cytokines. The increased number of autophagosomes in FSP1‐stimulated group and fewer autophagic corpuscles in siRNA‐FSP1 group was observed by transmission electron microscope (TEM). Autophagy‐related proteins (LC3B, beclin‐1 and Apg7) were higher in FSP1 group than those in other groups. Conversely, the expression of p62 protein was shown an opposite trend of variation. Therefore, these pathways can promote AFs bioactivity, facilitate autophagy and induce the expression of the proinflammatory cytokines. Contrarily, siRNA‐FSP1 intercepts the crosstalk of these pathways, suppresses AF functions, restrains autophagy and attenuates the expression of the inflammatory factors. Our findings indicate that crosstalk among RAGE, STAT3/JAK2 and Wnt3a/β‐catenin signalling pathways may account for the mechanism of AF functions with the stimulation of FSP1.

EPS364, a Novel Deep-Sea Bacterial Exopolysaccharide, Inhibits Liver Cancer Cell Growth and Adhesion

“…CTNNB1 is generally considered as an intermediate regulator molecule of the FGF19-FGFR4 signaling pathway [ 28 , 36 , 37 , 38 ]. In addition, a lot of studies have shown that the downregulation of CTNNB1 was associated with the downregulations of CDH2, ALCAM and ICAM1, which is consistent with our results [ 31 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. The extracellular FGF19-FGFR4 signaling pathway mediates the expression of cell adhesion molecules and regulates specific tumorigenic events, including cancer cell proliferation and metastasis, by activating the expression of downstream intracellular genes [ 35 , 49 , 50 ].…”

“…Studies have shown that the FGF19-FGFR4 signaling pathway was an effective antitumor target via mediating a lot of intracellular molecules [ 52 , 53 ]. CTNNB1 as an intermediate molecule between the FGF19-FGF4 signaling pathway and adhesion molecules such as ICAM1, CDH2 and ALCAM [ 31 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 58 ] was downregulated after EPS364 treatment. Hence, we speculated that EPS364 might target the FGF19-FGF4 signaling pathway to regulate the expression of adhesion molecules.…”

Moderate mechanical stress suppresses the IL‐1β‐induced chondrocyte apoptosis by regulating mitochondrial dynamics

“…TEM is an important method for the characterization of autophagosomes as it can directly visualize their inner architecture. The procedure was performed as previously described (Fu et al, 2019). In brief, the cells were washed with PBS and resuspended, and then post-fixed by 2% OsO 4 (Electron Microscopy Sciences), dehydrated with different concentrations of alcohol and acetone, and then embedded in epoxy resin.…”

Chloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE/STAT3 Pathway

“…In accordance with our findings, previous studies indicated that anticancer agents inhibited tumor growth, induced autophagy, and suppressed the JAK2/STAT3 pathway, while the autophagy inhibitor CQ enhanced this effect [42][43][44][45]; however, the mechanisms remain unclear, because the RAGE and STAT3 pathways are also regulated by various factors, including HMGB1, NF-κB, fibroblast-specific protein 1 (FSP1), SOCS3, CXCR3, etc. [46][47][48][49][50]. This could partially explain how PT combined with CQ might affect a complicated network in cells when regulating the RAGE and STAT3 pathways.…”