The interplay between fibroblast‐like synovial and vascular endothelial cells leads to angiogenesis via the sphingosine‐1‐phosphate‐induced RhoA‐F‐Actin and Ras‐Erk1/2 pathways and the intervention of geniposide

Citations Over TimeTop 19% of 2021 papers

Abstract

The changes of fibroblast-like synoviocytes (FLSs) and vascular endothelial cells (VECs) biological functions are closely related to angiogenesis in rheumatoid arthritis (RA). Nevertheless, how the crosstalk between FLSs and VECs interferes with RA is far from being clarified. Herein, we studied the effect of the reciprocal interactions between FLSs and VECs on angiogenesis and mechanism of geniposide (GE). After administration of GE, improvement of synovial hyperplasia in adjuvant arthritis rats was accompanied by downregulation of SphK1 and p-Erk1/2. The dynamic interaction between FLSs and VECs triggers the release of S1P by activating p-Erk1/2 and SphK1, then activating RhoA-F-actin and Ras-Erk1/2 pathways. When exposed to the inflammatory microenvironment mediated by FLSs-VECs crosstalk, proliferation, migration, and permeability of VECs were enhanced, the angiogenic factors were imbalanced. Meanwhile, the proliferation and secretory ability of FLSs increased. Interestingly, depletion of S1P or blocking of the activation of SphK1 by GE and PF-543 prevented the changes. In conclusion, S1P released during FLSs-VECs crosstalk changed their biological functions by activating RhoA-F-actin and Ras-Erk1/2 pathways. GE acted on p-Erk1/2 and SphK1, inhibited the secretion of S1P, and blocked the interplay between FLSs and VECs. These results provide new insights into the mechanism of angiogenesis in RA.

Related Papers

• → Overexpression of RhoA promotes the proliferation and migration of cervical cancer cells(2014)46 cited
• → RhoA regulates Schwann cell differentiation through JNK pathway(2018)31 cited
• → Tyr42 phosphorylation of RhoA GTPase promotes tumorigenesis through nuclear factor (NF)-κB(2017)28 cited
• → Quantitation of RhoA activation: differential binding to downstream effectors(2022)5 cited
• Function of the post-translationally modified C-terminal region of rho p21.(1992)