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CCN3 suppresses TGF-β1-induced extracellular matrix accumulation in human mesangial cells in vitro. 2018

Hai-Fei Liu, and Hong Liu, and Lin-Li Lv, and Kun-Ling Ma, and Yi Wen, and Long Chen, and Bi-Cheng Liu
Department of Nephrology, Taizhou First People's Hospital, Taizhou 225300, China.

Glomerular sclerosis is characterized by mesangial cell proliferation and progressive extracellular matrix (ECM) accumulation. CCN3 belongs to the CCN family of matrix proteins; increasing evidence suggests that CCN3 is an endogenous negative regulator of the ECM and fibrosis. However, the exact role of CCN3 in the accumulation of ECM remains unknown. The aim of the present study was to investigate the effects of CCN3 on TGF-β1-induced production of ECM in human mesangial cells (HMCs) in vitro. Treatment with TGF-β1 (0.5-2.0 ng/mL) suppressed the mRNA and protein expression of CCN3 in HMCs in dose- and time-dependent manners. Furthermore, treatment with TGF-β1 significantly increased the expression of the two markers of renal fibrosis, fibronectin (FN) and type I collagen (COLI), in HMCs. Moreover, treatment with TGF-β1 significantly decreased the expression of metalloproteinase (MMP)-2 and MMP-9, and markedly increased the expression of tissue inhibitor of metalloproteinase (TIMP)-1 in HMCs. Pretreatment of HMCs with exogenous CCN3 (5-500 ng/mL) or overexpression of CCN3 significantly attenuated TGF-β1-induced changes in FN, COLI, MMP-2, MMP-9 and TIMP-1 in HMCs. These results suggest that CCN3 suppresses TGF-β1-induced accumulation of ECM in HMCs. CCN3 may have potential as a novel therapeutic target for alleviating glomerulosclerosis.

UI MeSH Term Description Entries
D005109 Extracellular Matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
D005353 Fibronectins Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. Cold-Insoluble Globulins,LETS Proteins,Fibronectin,Opsonic Glycoprotein,Opsonic alpha(2)SB Glycoprotein,alpha 2-Surface Binding Glycoprotein,Cold Insoluble Globulins,Globulins, Cold-Insoluble,Glycoprotein, Opsonic,Proteins, LETS,alpha 2 Surface Binding Glycoprotein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D015854 Up-Regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Up-Regulation,Upregulation,Up-Regulation (Physiology),Up Regulation
D050527 Mesangial Cells Smooth muscle-like cells adhering to the wall of the small blood vessels of the KIDNEY at the glomerulus and along the vascular pole of the glomerulus in the JUXTAGLOMERULAR APPARATUS. They are myofibroblasts with contractile and phagocytic properties. These cells and their MESANGIAL EXTRACELLULAR MATRIX constitute the GLOMERULAR MESANGIUM. Glomerular Mesangial Cells,Extraglomerular Mesangial Cells,Lacis Cells,Mesangial Cells, Kidney,Renal Glomerulus Mesangial Cells,Renal Mesangial Cells,Cell, Extraglomerular Mesangial,Cell, Glomerular Mesangial,Cell, Kidney Mesangial,Cell, Lacis,Cell, Mesangial,Cell, Renal Mesangial,Cells, Extraglomerular Mesangial,Cells, Glomerular Mesangial,Cells, Kidney Mesangial,Cells, Lacis,Cells, Mesangial,Cells, Renal Mesangial,Extraglomerular Mesangial Cell,Glomerular Mesangial Cell,Kidney Mesangial Cell,Kidney Mesangial Cells,Lacis Cell,Mesangial Cell,Mesangial Cell, Extraglomerular,Mesangial Cell, Glomerular,Mesangial Cell, Kidney,Mesangial Cell, Renal,Mesangial Cells, Extraglomerular,Mesangial Cells, Glomerular,Mesangial Cells, Renal,Renal Mesangial Cell
D053773 Transforming Growth Factor beta1 A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME. TGF-beta1,Transforming Growth Factor-beta1,TGF-beta-1,TGF-beta1 Latency-Associated Protein,TGF-beta1LAP,Transforming Growth Factor beta 1 Latency Associated Peptide,Transforming Growth Factor beta I,Latency-Associated Protein, TGF-beta1,TGF beta 1,TGF beta1 Latency Associated Protein,TGF beta1LAP
D055514 Nephroblastoma Overexpressed Protein A CCN protein family member found at high levels in NEPHROBLASTOMA cells. It is found both intracellularly and in the EXTRACELLULAR MATRIX and may play a role in the regulation of CELL PROLIFERATION and EXTRACELLULAR MATRIX synthesis. CCN3 Protein,IGFBP9 Protein,NOVH Protein,Nephroblastoma Overexpressed Gene Product
D020778 Matrix Metalloproteinase 2 A secreted endopeptidase homologous with INTERSTITIAL COLLAGENASE, but which possesses an additional fibronectin-like domain. Gelatinase A,72-kDa Gelatinase,72-kDa Type IV Collagenase,MMP-2 Metalloproteinase,MMP2 Metalloproteinase,Matrix Metalloproteinase-2,72 kDa Gelatinase,72 kDa Type IV Collagenase,Gelatinase, 72-kDa,MMP 2 Metalloproteinase,Metalloproteinase 2, Matrix,Metalloproteinase, MMP-2,Metalloproteinase, MMP2

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