Proteoglycans of uterine fibroids and keloid scars: similarity in their proteoglycan composition

2012 ◽  
Vol 443 (2) ◽  
pp. 361-368 ◽  
Author(s):  
David A. Carrino ◽  
Sam Mesiano ◽  
Nichole M. Barker ◽  
William W. Hurd ◽  
Arnold I. Caplan
Keyword(s):  
Extracellular Matrix ◽  
Connective Tissue ◽  
Transforming Growth Factor ◽  
Uterine Fibroids ◽  
Transforming Growth Factor Β ◽  
Structural Support ◽  
Normal Tissues ◽  
Matrix Deposition ◽  
Keloid Scars ◽  
Extracellular Matrix Deposition

Fibrosis is the formation of excess and abnormal fibrous connective tissue as a result of either a reparative or reactive process. A defining feature of connective tissue is its extracellular matrix, which provides structural support and also influences cellular activity. Two common human conditions that result from fibrosis are uterine fibroids (leiomyomas) and keloid scars. Because these conditions share a number of similarities and because their growth is due primarily to excessive extracellular matrix deposition, we compared the proteoglycans of uterine fibroids and keloid scars with corresponding normal tissues. Our analysis indicates that uterine fibroids and keloid scars contain higher amounts of glycosaminoglycans relative to normal myometrium and normal adult skin respectively. Proteoglycan composition is also different in the fibrotic tissues. Compared with unaffected tissues, uterine fibroids and keloid scars contain higher relative amounts of versican and lower relative amounts of decorin. There is also evidence for a higher level of versican catabolism in the fibrotic tissues compared with unaffected tissues. These qualitative and quantitative proteoglycan differences may play a role in the expansion of these fibroses and in their excessive matrix deposition and matrix disorganization, due to effects on cell proliferation, TGF (transforming growth factor)-β signalling and/or collagen fibril formation.

Carvacrol Ameliorates Transforming Growth Factor-β1-Induced Extracellular Matrix Deposition and Reduces Epithelial-Mesenchymal Transition by Regulating The Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway In Hk-2 Cells

2021 ◽  
Vol 19 (4) ◽  
pp. 501-507
Author(s):  
Yunhe Gu ◽  
Peiyao Guo ◽  
Guangbiao Xu
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β1 ◽  
Mesenchymal Transition ◽  
Matrix Deposition ◽  
Extracellular Matrix Deposition ◽  
Dose Dependent

Transforming growth factor-β1 promotes excessive extracellular matrix deposition and epithelial-mesenchymal transition of tubular epithelial cells, thus stimulating the progression of renal fibrosis. Carvacrol has been shown to alleviate cardiac and liver fibrosis and attenuate renal injury. However, the role of carvacrol on renal fibrosis has not been examined. First, measurements using Cell Counting Kit-8 showed that carvacrol reduced cell viability of tubular epithelial cell line HK-2 in a dose-dependent fashion. Second, transforming growth factor-β1 induced excessive extracellular matrix deposition in HK-2 cells with enhanced collagen I, collagen IV, and fibronectin expression. However, carvacrol decreased the expression of collagen I, collagen IV in a dose-dependent manner and fibronectin to attenuate the extracellular matrix deposition in HK-2. Third, carvacrol attenuated TGF-β1-induced decrease of E-cadherin and increase of snail, vimentin, and alpha-smooth muscle actin in HK-2 cells. Transforming growth factor-β1-induced increase in PI3K and AKT phosphorylation in HK-2 were also reversed by carvacrol. Collectively, carvacrol ameliorates renal fibrosis through inhibition of transforming growth factor-β1-induced extracellular matrix deposition and epithelial-mesenchymal transition of HK-2 cells, providing potential therapy for the treatment of renal fibrosis.

Long Noncoding RNA MIAT Modulates the Extracellular Matrix Deposition in Leiomyomas by Sponging MiR-29 Family

Endocrinology ◽  
2021 ◽  
Vol 162 (11) ◽  
Author(s):  
Tsai-Der Chuang ◽  
Derek Quintanilla ◽  
Drake Boos ◽  
Omid Khorram
Keyword(s):  
Extracellular Matrix ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Luciferase Reporter ◽  
Cycle Phase ◽  
Type I ◽  
Matrix Deposition

Abstract The objective of this study was to determine the expression and functional role of a long noncoding RNA (lncRNA) MIAT (myocardial infarction–associated transcript) in leiomyoma pathogenesis. Leiomyoma compared with myometrium (n = 66) expressed significantly more MIAT that was independent of race/ethnicity and menstrual cycle phase but dependent on MED12 (mediator complex subunit 12) mutation status. Leiomyomas bearing the MED12 mutation expressed higher levels of MIAT and lower levels of microRNA 29 family (miR-29a, -b, and -c) compared with MED12 wild-type leiomyomas. Using luciferase reporter activity and RNA immunoprecipitation analysis, MIAT was shown to sponge the miR-29 family. In a 3-dimensional spheroid culture system, transient transfection of MIAT siRNA in leiomyoma smooth muscle cell (LSMC) spheroids resulted in upregulation of miR-29 family and downregulation of miR-29 targets, collagen type I (COL1A1), collagen type III (COL3A1), and TGF-β3 (transforming growth factor β-3). Treatment of LSMC spheroids with TGF-β3 induced COL1A1, COL3A1, and MIAT levels, but repressed miR-29 family expression. Knockdown of MIAT in LSMC spheroids blocked the effects of TGF-β3 on the induction of COL1A1 and COL3A1 expression. Collectively, these results underscore the physiological significance of MIAT in extracellular matrix accumulation in leiomyoma.

Existence of a regulatory loop between MCP-1 and TGF-β in glomerular immune injury

2002 ◽  
Vol 283 (5) ◽  
pp. F1075-F1084 ◽  
Author(s):  
Gunter Wolf ◽  
Thomas Jocks ◽  
Gunther Zahner ◽  
Ulf Panzer ◽  
Rolf A. K. Stahl
Keyword(s):  
Extracellular Matrix ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Glomerular Injury ◽  
Rat Serum ◽  
Matrix Deposition ◽  
Β Protein ◽  
Chemotactic Protein ◽  
Early Expression ◽  
Regulatory Loop

Glomerular upregulation of monocyte chemotactic protein-1 (MCP-1), followed by an influx of monocytes resulting eventually in extracellular matrix deposition is a common sequel of many types of glomerulonephritis. However, it is not entirely clear how early expression of MCP-1 is linked to the later development of glomerulosclerosis. Because transforming growth factor-β (TGF-β) is a key regulator of extracellular matrix proteins, we hypothesized that there might be a regulatory loop between early glomerular MCP-1 induction and subsequent TGF-β expression. To avoid interference with other cytokines that may be released from infiltrating monocytes, isolated rat kidneys were perfused with a polyclonal anti-thymocyte-1 antiserum (ATS) and rat serum (RS) as a complement source to induce glomerular injury. Renal TGF-β protein and mRNA expressions were strongly stimulated after perfusion with ATS-RS. This effect was attenuated by coperfusion with a neutralizing anti-MCP-1 but was partly mimicked by perfusion with recombinant MCP-1 protein. On the other hand, renal MCP-1 expression and production were stimulated by administration of ATS-RS. Additional perfusion with an anti-TGF-β antibody further aggravated this increase, whereas application of recombinant TGF-β protein reduced MCP-1 formation. Our data demonstrate an intrinsic regulatory loop in which increased MCP-1 levels stimulate TGF-β formation in resident glomerular cells in the absence of infiltrating immune competent cells.

Extracellular matrix deposition by primary human lung fibroblasts in response to TGF-β1 and TGF-β3

1999 ◽  
Vol 276 (5) ◽  
pp. L814-L824 ◽  
Author(s):  
Oliver Eickelberg ◽  
Eleonore Köhler ◽  
Frank Reichenberger ◽  
Sybille Bertschin ◽  
Thomas Woodtli ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Transforming Growth Factor ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Matrix Deposition ◽  
Proline Incorporation ◽  
Primary Fibroblasts ◽  
Extracellular Matrix Deposition ◽  
Tgf Β1

Increased collagen and extracellular matrix (ECM) deposition within the lung is a characteristic feature of lung fibrosis. Transforming growth factor (TGF)-β isoforms play a pivotal role in the production of collagen and ECM. In this study, we investigated the effects of TGF-β1 and TGF-β3 on the main processes controlling ECM deposition using primary human lung fibroblasts. We analyzed 1) collagen metabolism by [3H]proline incorporation, 2) matrix metalloproteinase (MMP) expression by substrate gel zymography, and 3) tissue inhibitor of metalloproteinases (TIMP) expression by Western blot analysis. TGF-β1 and TGF-β3 increased the percentage of secreted collagens in supernatants of primary fibroblasts from 8.0 ± 1.2 (control) to 23.6 ± 4.6 and 22.3 ± 1.3%, respectively. The collagen percentage in deposited ECM was increased from 5.8 ± 0.3 (control) to 9.0 ± 0.5 and 8.8 ± 0.5% by TGF-β1 and TGF-β3, respectively. Secretion of MMP-1 (interstitial collagenase) by fibroblasts was reduced by both TGF-β isoforms, whereas secretion of MMP-2 (gelatinase A) was unaffected by either of the two isoforms. Both TGF-β isoforms increased TIMP-1 protein expression, whereas TIMP-2 protein was decreased. We thus conclude that TGF-β1 and TGF-β3 are equally potent in increasing ECM deposition. Their fibrotic effect in lung fibroblasts results from 1) an increase in the secretion and deposition of total ECM and collagens, 2) a decrease in MMP-1 secretion, and 3) an increase of TIMP-1 expression.

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