title: CCN4 induces vascular cell adhesion molecule-1 expression in human synovial fibroblasts and promotes monocyte adhesion.
abstract: CCN4 is a cysteine-rich protein that belongs to the Cyr61, CTGF, Nov family of matricellular proteins. Here, we investigated the intracellular signaling pathways involved in CCN4-induced vascular cell adhesion molecule-1 expression in human osteoarthritis synovial fibroblasts. Stimulation of OASFs with CCN4 induced VCAM-1 expression. CCN4-induced VCAM-1 expression was attenuated by αvβ5 or α6β1 integrin antibody, Syk inhibitor, PKCδ inhibitor (rottlerin), JNK inhibitor (SP600125), and AP-1 inhibitors (curcumin and tanshinone). Stimulation of cells with CCN4 increased Syk, PKCδ, and JNK activation. Treatment of OASFs with CCN4 also increased c-Jun phosphorylation, AP-1-luciferase activity, and c-Jun binding to the AP-1 element in the VCAM-1 promoter. Moreover, up-regulation of VCAM-1 increased the adhesion of monocytes to OASF monolayers, and this adhesion was attenuated by transfection with a VCAM-1 siRNA. Our results suggest that CCN4 increases VCAM-1 expression in human OASFs via the Syk, PKCδ, JNK, c-Jun, and AP-1 signaling pathways. The CCN4-induced VCAM-1 expression promoted monocyte adhesion to human OASFs.
authors: Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors: Ju-Fang
authors: JF
authors: Liu
authors: Sheng-Mou
authors: SM
authors: Hou
authors: Chun-Hao
authors: CH
authors: Tsai
authors: Chun-Yin
authors: CY
authors: Huang
authors: Chin-Jung
authors: CJ
authors: Hsu
authors: Chih-Hsin
authors: CH
authors: Tang
mesh_terms: D055511:CCN Intercellular Signaling Proteins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D055515:Cysteine-Rich Protein 61 / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D055514:Nephroblastoma Overexpressed Protein / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D055511:CCN Intercellular Signaling Proteins; C501848:CCN1 protein, human; C526317:CCN2 protein, human; C526319:CCN3 protein, human; C116396:CCN4 protein, human; D055515:Cysteine-Rich Protein 61; D055514:Nephroblastoma Overexpressed Protein; D011518:Proto-Oncogene Proteins; D019010:Vascular Cell Adhesion Molecule-1; D055513:Connective Tissue Growth Factor