TGF-??1 Reverses the Effects of Matrix Anchorage on the Gene Expression of Decorin and Procollagen Type I in Tendon Fibroblasts

2005 ◽  
Vol &NA; (431) ◽  
pp. 226-232 ◽  
Author(s):  
Sai-Chuen Fu ◽  
Yim-Ping Wong ◽  
Yau-Chuk Cheuk ◽  
Kwong-Man Lee ◽  
Kai-Ming Chan
2005 ◽  
Vol 152 (2) ◽  
pp. 242-249 ◽  
Author(s):  
A.M. deGiorgio-Miller ◽  
L.J. Treharne ◽  
R.J. McAnulty ◽  
P.D. Coleridge Smith ◽  
G.J. Laurent ◽  
...  

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P189-P189
Author(s):  
Tsunehisa Ohno ◽  
Lesley C. French ◽  
Bernard Rousseau

Problem The authors investigated the expression of key extracellular matrix genes after vocal fold wounding in a rat model to better understand the reparative mechanisms of tissue repair during the remodeling phase of vocal fold injury. Methods Bilateral vocal fold wounds were created in 30 rats. Injured vocal fold specimens were harvested 1, 3, 7, 14, 28, and 56 days after wounding. 5 unwounded rats were used to establish baseline for polymerase chain reaction (PCR). The authors used real-time PCR to quantify messenger RNA expression of procollagen type I, III, interleukin-1 beta (IL-1 beta), decorin, and hyaluronan synthase (HAS) −1, −2, and −3. Analysis of variance was used to detect main effects for gene expression. Post-hoc tests were used to make comparisons between time points. Results Procollagen type I expression was decreased from baseline on post-injury day 1, 28, and 56. Procollagen type III was decreased on post-injury day 1 and 56, and increased from baseline on post-injury day 14. IL-1 beta expression was increased from baseline on post-injury day 1, 3, and 7. Decorin expression was decreased from baseline on post-injury day 1, 3, 7, and 56. HAS-1 expression was decreased from baseline at all post-injury time points. HAS-2 expression was increased from baseline on post-injury day 3, and decreased from baseline on post-injury day 14, 28, and 56. HAS-3 expression was decreased from baseline on post-injury day 1, 28, and 56. Conclusion Findings provide temporal changes in the expression of key extracellular matrix genes during a remodeling phase of vocal fold injury in a rat wound model. Significance Vocal fold wound models provide a means for investigating tissue reparative processes and molecular mechanisms controlling synthesis and degradation of the vocal fold extracellular matrix. Support Vanderbilt University Medical Center.


Author(s):  
W Grant Stevens ◽  
Daniel J Gould ◽  
Linda D Pham ◽  
Joel N Jimenez Lozano

Abstract Background In addition to body contouring, there is anecdotal and supportive clinical evidence of reduced laxity and skin tightening after cryolipolysis. 10,11 Objectives The nature by which cryolipolysis triggers dermal changes has not been established. This study investigated fundamental mechanisms behind clinically observed dermal changes using molecular and immunohistochemistry methods. Methods This feasibility study involved n=7 subjects that received cryolipolysis treatment. Tissue samples were harvested from 3 days to 5 weeks after treatment. RNA-Sequencing examined differential gene expression of major collagens. RNA In Situ Hybridization (RNA-ISH) investigated the distribution of one of the gene markers for collagen Type I (COL1A1). Immunohistochemistry for Procollagen Type I, heat shock protein 47 (HSP47), transforming growth factor beta (TGF-β and Tropoelastin was performed and quantified. Results Gene expression analysis highlighted a gradual upregulation of collagen mRNA genes. RNA-ISH confirmed upregulation of COL1A1 mRNA and showed a homogenous distribution through the dermis. Immunohistochemistry showed increases in protein expression. Quantification revealed 3.62-fold increase of Procollagen Type I (p<0.0071) and 2.91-fold increase of TGF-β (p<0.041); 1.54-fold increase of HSP47 (p<0.007); and 1.57-fold increase of Tropoelastin (p<0.39) compared to untreated areas. Conclusions This study revealed significant induction of molecular and protein markers of Type I collagen, which supports neocollagenesis and may play an essential role in clinically relevant skin improvement. A dermal remodeling process driven by increased TGF-β and higher expression of HSP47 was observed. Overall, these data provide the first evidence of dermal remodeling and clarify the mechanism by which cryolipolysis may induce skin improvement.


1995 ◽  
Vol 108 (1) ◽  
pp. 145-156 ◽  
Author(s):  
Giuseppe Malizia ◽  
Elizabeth M. Brunt ◽  
Marion G. Peters ◽  
Aroldo Rizzo ◽  
Thomas J. Broekelmann ◽  
...  

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Katarzyna A Cieslik ◽  
JoAnn Trial ◽  
Mark L Entman

In the aging mouse (C57BL/6) myocardium fibrosis steadily increases after 14 months of age and is accompanied by elevated numbers of myeloid derived fibroblasts. Recently, we proposed a mechanism by which inflammatory mesenchymal fibroblasts (IMF) derived from mesenchymal stem cells secrete monocyte chemoattractant protein-1 (MCP-1) necessary for myeloid fibroblast induction in the aging heart. The current study extends the characterization of this inflammatory phenotype by describing elevated interleukin-6 (IL-6) secretion and increased expression of IL-6 receptor (IL-6R) in IMF. Since IL-6R lacks an intracellular domain it requires a co-receptor gp130 (generally expressed) to induce an intracellular signal. Thus, generation of an IL-6R soluble receptor allows IL-6 signaling on cells that do not express IL-6R (or expression is low), such as endothelial cells. We investigate the function of IL-6 and IL-6R in the promotion of transendothelial migration of monocytes through cardiac endothelium and their maturation into myeloid fibroblasts in in vitro assay. Treatments with IL-6 and more extensively IL-6+IL-6R resulted in a 3-5 fold increase (above the control level) in myeloid cell migration and maturation into myeloid fibroblasts. Thus IMF can contribute both IL-6 and IL-6R to endothelial cells and facilitate myeloid cell transendothelial migration. In agreement with these data, analysis of the aged mouse heart revealed the presence of fibroblasts expressing IL-6 (procollagen type I + IL-6 + cells), M1 macrophages (CD86 + cells) and M2 macrophages (CD301 + procollagen type I + cells) that were absent in hearts from young mice. The mechanisms by which expression of these factors is upregulated in IMF are being investigated; our data suggest that MCP-1 and IL-6 expression are controlled by the farnesyltransferase (FTase)-Ras-Erk1/2 pathway. Interestingly, since atorvastatin interferes with farnesyl synthesis it also reduced MCP-1 and IL-6 expression in IMF. These data may introduce a new use of this class of drugs in the prevention of the age-related fibrosis.


1994 ◽  
Vol 130 (4) ◽  
pp. 381-386 ◽  
Author(s):  
Moustapha Kassem ◽  
Leif Mosekilde ◽  
Erik F Eriksen

Kassem M, Mosekilde L, Eriksen EF. Effects of fluoride on human bone cells in vitro: differences in responsiveness between stromal osteoblast precursors and mature osteoblasts. Eur J Endocrinol 1994;130:381–6. ISSN 0804–4643 The cellular effects of sodium fluoride (NaF) on human bone cells in vitro have been variable and dependent on the culture system used. Variability could be attributed to differences in responsiveness to NaF among different populations of cells at various stages of differentiation in the osteoblastic lineage. In this study we compared the effects of NaF in serum-free medium on cultures of more differentiated human osteoblast-like (hOB) cells derived from trabecular bone explants and on osteoblast committed precursors derived from human bone marrow, i.e. human marrow stromal osteoblast-like (hMS(OB)) cells. Sodium fluoride (10−5 mol/l) increased proliferation of hMS(OB) cells (p<0.05, N = 10) but was not mitogenic to hOB cells (p>0.05, N= 10). Alkaline phosphatase (AP) production increased in both hMS(OB) (p<0.05, N=9) and hOB cells (p<0.05, N=9). No significant effects on procollagen type I propeptide production were obtained in either culture. In the presence of 1,25-dihydroxycholecalciferol (10−9 mol/l), NaF enhanced alkaline phosphatase (p<0.05, N=8), procollagen type I propeptide (p<0.05, N=7) and osteocalcin (p<0.05, N=7) production by hMS(OB) cells but not by hOB cells. Our results suggest that osteoblast precursors are more sensitive to NaF action than mature osteoblasts and that the in vivo effects of NaF on bone formation may be mediated by stimulating proliferation and differentiation of committed osteoblast precursors in bone marrow. M Kassem, Mayo Clinic, Endocrine Research Unit, W-Joseph 5-164, Rochester, MN 55904, USA


Dermatology ◽  
1995 ◽  
Vol 190 (2) ◽  
pp. 104-108 ◽  
Author(s):  
K. Kikuchi ◽  
T. Kadono ◽  
M. Fujimoto ◽  
H. Ihn ◽  
S. Sato ◽  
...  

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Eddy Barasch ◽  
John S Gottdiener

Background: The fibrillar myocardial extracellular matrix is mainly composed of type I and III fibrillar collagen and their turnover are reflected in the serum level of carboxyl-terminal propeptide type I (PIP) and procollagen type III aminoterminal peptide (PIIINP). The prognostic value of these biomarkers in elderly individuals with heart failure (HF) or other cardiovascular disease (CVD) and in healthy subjects is largely unknown. Aim: To determine the predictive value of PIP, its degradation metabolite, carboxyterminal telopeptide of procollagen type I (CTIP), and PIIINP serum level for the incident CV morbidity and mortality in a nested case control study of community-dwelling elderly individuals enrolled in the Cardiovascular Health Study (CHS). Methods: In 880 participants (ppts) enrolled in the CHS (mean age 77 ± 6 yrs, 52 % males, 79 % white), 310 with HF, 287 controls (no HF but other CVD) and 283 healthy ppts, serum levels of PIIINP, PIP and CTIP were measured by radioimmunoassay. The number of incident CV disease and death were recorded. Wilcoxon rank sum test, Kruskal-Wallis test, and Cox proportional hazards regression were used as appropriate. Results: Age, gender and race and fully adjusted analyses are presented in the table : Conclusions: In this large elderly cohort, there is a strong association between CTIP, PIIINP and incident CVD and death. Elevated CTIP level increases the risk of death more than 50% and of symptomatic PVD by almost two-fold. Whereas PIIINP has a lower predictive power than CTIP, PIP was not associated with incident CVD or death. Serum CTIP and PIIINP have a good prognostic value for both incident CVD and death in elderly individuals with or without known CV disease.


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