The Matricellular Protein Cyr61 Is a Key Mediator of Platelet-derived Growth Factor-induced Cell Migration

Abstract

Background: PDGF is a potent chemoattractant for cells. Results:The PDGF-induced extracellular matrix component Cyr61 bridges the intracellular PDGF-ERK and JNK signaling pathways with integrin/FAK signaling, leading to cell migration. Conclusion: Cyr61 is a key mediator of PDGF-induced cell migration via the Cyr61-integrin-FAK pathway. Significance: Extracellular Cyr61 convergence with growth factor and integrin/FAK signaling is a new cell migration concept.

DDR2–CYR61–MMP1 Signaling Pathway Promotes Bone Erosion in Rheumatoid Arthritis Through Regulating Migration and Invasion of Fibroblast-Like Synoviocytes

“…CYR61 is a secreted matricellular protein that associates with the cell surface and the extracellular matrix via binding to integrins or heparan sulfate proteoglycans . Functionally, CYR61 mediates cell proliferation, adhesion, migration, and differentiation and promotes angiogenesis . CYR61 has been implicated in a myriad of disease processes, including RA pathogenesis.…”

“…Among them, cysteine‐rich protein 61 ( CYR61 ) was one of the most highly upregulated mRNAs. CYR61, a member of the CCN‐family, is involved in the adhesion, proliferation, and migration of various tumor cell lines. Recently, a few studies have implicated that elevated CYR61 expression in RA patients promotes the secretion of IL‐1β, IL‐6, and IL‐8 by FLS and regulates FLS proliferation and Th17 cell differentiation .…”

Evaluation of Serum Cysteine-Rich Protein 61 levels in Patients with Coronary Artery Disease

“…CRP is an acute phase reactant and its secretion begins within 4-6 h of the stimulus and peaks at about 36-48 h. CRP is widely used and recognized as valuable biomarker in cardiovascular risk and events assessment. As an inducible immediate early gene, Cyr61 syntheses is increased by numerous atherogenic factors maximally at 1-3 h [13,19,26,30,43], we found Cyr61 is significantly increased maximally at 2 h with lasting more than 8 h in high level after stimulation by angiotensin II and thrombin in human aortic smooth muscle cells [deng, unpublished data], indicating the change of Cyr61 precedes CRP in rise and peaking. Therefore, Cyr61 holds promising value as a biomarker candidate in CAD diagnosis, risk stratification and monitoring therapeutic efficacy and prognosis than CRP does.…”

“…The initial and key step for atherogenesis is endothelial inflammation and leukocytes recruitment and infiltration [37], thus, elevated serum Cyr61 levels in patients with CAD is consistent with the concept of inflammatory mechanisms in atherosclerosis pathogenesis and reflects atherosclerosis development and progression. In addition, Cyr61 was reported to support vascular smooth muscle cells (VSMCs) adhesion and stimulate proliferation and migration [19,38], this effect may also involve the recruitment of VSMCs from the tunica media into the tunica intima to accelerate atheroma formation and vascular narrowing. Therefore, Cyr61 may be implicated in different stage of atherosclerosis.…”

“…Studies demonstrated that Cyr61 is increased after vascular injury and higher level of Cyr61 is reported in atherosclerostic lesions [12][13][14]. The expression of Cyr61 is at a very low level in quiescent condition, but is highly expressed within minutes or hours after stimulation by numerous atherogenic factors or extracellular stimuli including VEGF, PDGF, bFGF, TGF-β, growth hormone, angiotensin II, thrombin, inflammatory cytokines, hs-CRP and hypoxia, mechanical stretch [15,[18][19][20][21][22][23][24][25][26][27][28][29][30]. A variety of cell types including endothelial and epithelial cells, vascular smooth muscle cells, fibroblasts, monocytes, activated platelets and cardiomyocytes have been identified as sources of Cyr61 [11][12][13][14][15][16]18,28,31].…”