Marked attenuation of production of collagen type I from cardiac fibroblasts by dehydroepiandrosterone

2005 ◽  
Vol 288 (6) ◽  
pp. E1222-E1228 ◽  
Author(s):  
Tomoyuki Iwasaki ◽  
Koji Mukasa ◽  
Masato Yoneda ◽  
Satoshi Ito ◽  
Yoshihiko Yamada ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Protein Accumulation ◽  
Transcriptional Level ◽  
Type I ◽  
Procollagen Type ◽  
Procollagen Type I

Dehydroepiandrosterone (DHEA) is a type of adrenal steroid. The concentrations of DHEA and its sulfate (DHEA-S) in serum reach a peak between the ages of 25 and 30 yr and thereafter decline steadily. It was reported that DHEA-S concentration in humans is inversely related to death from cardiovascular diseases. In this study, we examined the effects of DHEA on regulation of collagen mRNA and collagen synthesis in cultured cardiac fibroblasts. Treatment with DHEA (10−6 M) resulted in a significant decrease in procollagen type I mRNA expression compared with controls. This was accompanied by a significant decrease in procollagen type I protein accumulation in the medium and also a significant decrease in procollagen type I protein synthesis in the cellular matrix. Furthermore, to confirm in vitro results, we administered DHEA to Sprague-Dawley rats, which were treated with angiotensin II for 8 wk to induce cardiac damage. Procollagen type I mRNA expression was significantly decreased and cardiac fibrosis significantly inhibited in DHEA-treated rat hearts without lowering the systolic blood pressure. These results strongly indicate that DHEA can directly attenuate collagen type I synthesis at the transcriptional level in vivo and in vitro in cardiac fibroblasts.

scholarly journals Mutations in COL1A1 and COL1A2 Genes Associated with Osteogenesis Imperfecta (OI) Types I or III.

2018 ◽  
Vol 65 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Aleksandra Augusciak-Duma ◽  
Joanna Witecka ◽  
Aleksander L. Sieroń ◽  
Magdalena Janeczko ◽  
Jacek J Pietrzyk ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Collagen Type ◽  
Collagen Type I ◽  
Base Substitution ◽  
Type I ◽  
Intracellular Accumulation ◽  
Single Base ◽  
Type Iii ◽  
Procollagen Type ◽  
Procollagen Type I

Over 85% of osteogenesis imperfecta (OI) cases associates to mutations in procollagen type I genes (COL1A1 or COL1A2), however, no hot spots were linked to particular clinical phenotypes. The 8 patients whom were clinically diagnosed with OI are from Polish population with no ethnic background indicated. Six unpublished mutations were detected in eight patients diagnosed with OI. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were also determined. In COL1A1 gene the mutations were found in exons 2, 22, 50 and in introns 13 and 51. In COL1A2 one mutation was identified in exon 22. Mutations of deletion type in COL1A1 that resulted in OI type I an effect neither on collagen type I secretion nor its intracellular accumulation were detected. Also, a single base substitution in I13 (c.904-9 G>T) was associated with OI type I. The OI type III was associated with single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly®Cys in the central part of triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation to procollagen type I. The results shall help in genetic counseling of OI patients and provide rational support in making by them and their families conscious, life important decisions.

scholarly journals Beneficial Effects of Mineralocorticoid Receptor Antagonism on Myocardial Fibrosis in an Experimental Model of the Myxomatous Degeneration of the Mitral Valve

2020 ◽  
Vol 21 (15) ◽  
pp. 5372
Author(s):  
Jaime Ibarrola ◽  
Mattie Garaikoetxea ◽  
Amaia Garcia-Peña ◽  
Lara Matilla ◽  
Eva Jover ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Myocardial Fibrosis ◽  
Mineralocorticoid Receptor ◽  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Type I ◽  
Myxomatous Degeneration ◽  
Human Cardiac Fibroblasts

Mitral valve prolapse (MVP) patients develop myocardial fibrosis that is not solely explained by volume overload, but the pathophysiology has not been defined. Mineralocorticoid receptor antagonists (MRAs) improve cardiac function by decreasing cardiac fibrosis in other heart diseases. We examined the role of MRA in myocardial fibrosis associated with myxomatous degeneration of the mitral valve. Myocardial fibrosis has been analyzed in a mouse model of mitral valve myxomatous degeneration generated by pharmacological treatment with Nordexfenfluramine (NDF) in the presence of the MRA spironolactone. In vitro, adult human cardiac fibroblasts were treated with NDF and spironolactone. In an experimental mouse, MRA treatment reduced interstitial/perivascular fibrosis and collagen type I deposition. MRA administration blunted NDF-induced cardiac expression of vimentin and the profibrotic molecules galectin-3/cardiotrophin-1. In parallel, MRA blocked the increase in cardiac non-fibrillar proteins such as fibronectin, aggrecan, decorin, lumican and syndecan-4. The following effects are blocked by MRA: in vitro, in adult human cardiac fibroblasts, NDF-treatment-induced myofibroblast activation, collagen type I and proteoglycans secretion. Our findings demonstrate, for the first time, the contribution of the mineralocorticoid receptor (MR) to the development of myocardial fibrosis associated with mitral valve myxomatous degeneration. MRA could be a therapeutic approach to reduce myocardial fibrosis associated with MVP.

Orthosilicic Acid Increases Collagen Type I mRNA Expression in Human Bone-Derived Osteoblasts In Vitro

2003 ◽  
Vol 254-256 ◽  
pp. 869-872 ◽  
Author(s):  
Meera Q. Arumugam ◽  
D.C. Ireland ◽  
Roger A. Brooks ◽  
Neil Rushton ◽  
William Bonfield
Keyword(s):  
Mrna Expression ◽  
Collagen Type ◽  
Collagen Type I ◽  
Human Bone ◽  
Orthosilicic Acid ◽  
Type I

The Effect Orthosilicic Acid on Collagen Type I, Alkaline Phosphatase and Osteocalcin mRNA Expression in Human Bone-Derived Osteoblasts In Vitro

2006 ◽  
Vol 309-311 ◽  
pp. 121-124 ◽  
Author(s):  
Meera Q. Arumugam ◽  
D.C. Ireland ◽  
Roger A. Brooks ◽  
Neil Rushton ◽  
William Bonfield
Keyword(s):  
Alkaline Phosphatase ◽  
Mrna Expression ◽  
Messenger Rna ◽  
Collagen Type ◽  
Collagen Type I ◽  
Orthosilicic Acid ◽  
Type I ◽  
Mrna Levels ◽  
Polymerase Chain

The object of this study was to investigate the effect of the concentration of orthosilicic acid (0, 0.5, 1, 5 and 10µM) on gene expression in human osteoblast cells isolated from trabecular bone. This was measured using reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify messenger RNA (mRNA) levels for collagen type I, alkaline phosphatase and osteocalcin. Results showed that while collagen type I mRNA expression was increased by the addition of up to 10µM orthosilicic acid, ALP message was suppressed over time and osteocalcin levels were decreased.

scholarly journals Pheophorbide a Derivatives Exert Antiwrinkle Effects on UVB-Induced Skin Aging in Human Fibroblasts

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 147
Author(s):  
Hwa Lee ◽  
Ho-Yong Park ◽  
Tae-Sook Jeong
Keyword(s):  
Mrna Expression ◽  
Human Fibroblasts ◽  
Collagen Type I ◽  
Skin Aging ◽  
Breakdown Product ◽  
Type I ◽  
Pheophorbide A ◽  
Procollagen Type ◽  
Procollagen Type I ◽  
Pyropheophorbide A

Pheophorbide a is a chlorophyll metabolic breakdown product. This study investigated the antiwrinkle effect of pheophorbide a (PA) and its derivatives, including pyropheophorbide a (PyroPA) and pyropheophorbide a methyl ester (PyroPA-ME), on ultraviolet (UV) B-stimulated CCD-986sk fibroblasts. PA, PyroPA, and PyroPA-ME effectively suppressed reactive oxygen species accumulation in UVB-exposed CCD-986sk fibroblasts. All three pheophorbides also reduced UVB-induced matrix metalloproteinase (MMP)-1 secretion and mRNA expression of MMP-1, MMP-2, and MMP-9. Treatment with pheophorbides resulted in increased procollagen synthesis, and this required enhancement of procollagen type I C-peptide content and mRNA expression of collagen type I alpha 1 (COL1A1) and COL1A2 in CCD-986sk cells. These antiwrinkle effects were more potent with PA and PyroPA than with PyroPA-ME. Furthermore, PA and PyroPA suppressed UVB-induced phosphorylation of extracellular signal-regulated protein kinase and c-Jun N-terminal kinase but not p38. Moreover, all three pheophorbides inhibited NF-κB p65 phosphorylation. Therefore, these pheophorbides, especially PA and PyroPA, can be used as antiwrinkle agents, and PA- or PyroPA-rich natural resources can be used in functional cosmetics.

scholarly journals P049 Development of human embryonic stem cell-derived intestinal organoids for in vitro studies on intestinal inflammation and fibrosis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S158-S158
Author(s):  
L Kandilogiannakis ◽  
E Filidou ◽  
I Drygiannakis ◽  
G Tarapatzi ◽  
K Arvanitidis ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Collagen Type ◽  
Embryonic Stem ◽  
Collagen Type I ◽  
Type I ◽  
Maturation Process ◽  
Type Iii ◽  
Intestinal Organoids ◽  
Tnf Α

Abstract Background Organoids are self-renewing, 3D structures, consisting of different cell types, with histology and physiology features very close to the physiology of the studied organ. Specifically, human Intestinal Organoids (HIOs) develop epithelial crypts consisting of all subtypes of intestinal epithelial cells which are surrounded by mesenchymal cells. Our aim was to develop 3D HIOs from human embryonic stem cells (hESCs) and examine the expression of fibrotic and mesenchymal factors during their maturation process. Additionally, we investigated the effect of the pro-inflammatory cytokines, IL-1α and TNF-α on the expression of fibrotic and inflammatory mediators in HIOs. Methods The human ESC line (H1) was cultured and then differentiated towards HIOs using commercially available kit. HIOs were characterized by immunofluorescence in all differentiation stages. In order to examine their maturation process, we compared the mRNA expression of fibrotic and mesenchymal markers from passages 1–10. In order to examine their functionality, HIOs from different passages were stimulated with 5ng/ml IL-1α and 50ng/ml TNF-α for 12 hours, total RNA was collected and the fibrotic and inflammatory mRNA expression was examined. The mRNA transcripts of CD90, collagen type I, III, fibronectin, CXCL8, CXCL10 and CXCL11 were measured by reverse transcription quantitative PCR. Results HIOs were successfully developed as they were stained positive for all tested markers throughout their developmental process. Regarding their maturation process, we observed high expression of CD90, collagen type I, type III and fibronectin that was gradually decreased during passages. As for the fibrotic and inflammatory responses from HIOs, we found that the IL-1α and TNF-α stimulation resulted in statistically significant upregulation of the fibrotic factors, fibronectin, collagen type I and type III in culture passages 2 and 4, but had no effect in culture passages 8 and 10. Similarly, IL-1α and TNF-α stimulation led to the statistically significant induction of the inflammatory chemokines CXCL8, CXCL10 and CXCL11 in culture passages 2 and 4, while no effect was observed in culture passages 8 and 10. Conclusion Our findings indicate that HIOs contain a functional mesenchymal component that is gradually diminished during passages. Inflammatory and fibrotic responses of HIOs seem to depend on the fitness of their mesenchyme. IBD studies using HIOs as in vitro models should be performed on early passages, when HIO’s mesenchymal component is still functional.

scholarly journals Relative rates of biosynthesis of collagen type I, type V and type VI in calf cornea

1991 ◽  
Vol 274 (2) ◽  
pp. 615-617 ◽  
Author(s):  
P Kern ◽  
M Menasche ◽  
L Robert
Keyword(s):  
Type I Collagen ◽  
Collagen Type ◽  
Corneal Stroma ◽  
Collagen Type I ◽  
Type I ◽  
Type Vi Collagen ◽  
Sds Page ◽  
Proline Incorporation ◽  
Type V

The biosynthesis of type I, type V and type VI collagens was studied by incubation of calf corneas in vitro with [3H]proline as a marker. Pepsin-solubilized collagen types were isolated by salt fractionation and quantified by SDS/PAGE. Expressed as proportions of the total hydroxyproline solubilized, corneal stroma comprised 75% type I, 8% type V and 17% type VI collagen. The rates of [3H]proline incorporation, linear up to 24 h for each collagen type, were highest for type VI collagen and lowest for type I collagen. From pulse-chase experiments, the calculated apparent half-lives for types I, V and VI collagens were 36 h, 10 h and 6 h respectively.

scholarly journals 14 Characterization of adipose tissue extracellular matrix component mRNA expression during porcine adipogenesis using real-time PCR

2020 ◽  
Vol 98 (Supplement_2) ◽  
pp. 35-35
Author(s):  
Maegan A Reeves ◽  
Courtney E Charlton ◽  
Terry D Brandebourg
Keyword(s):  
Extracellular Matrix ◽  
Adipose Tissue ◽  
Mrna Expression ◽  
Real Time ◽  
Real Time Pcr ◽  
Collagen Type ◽  
Primary Cultures ◽  
Collagen Type I ◽  
Type I ◽  
Matrix Metallopeptidase

Abstract Given adipose tissue is histologically classified as connective tissue, we hypothesized expression of extracellular matrix (ECM) components are significantly altered during adipogenesis. However, little is known about the regulation of the ECM during adipose tissue development in the pig. Therefore, the objective of this study was to characterize expression of ECM components during porcine adipogenesis. Primary cultures of adipose tissue stromal-vascular cells were harvested from 3-day-old neonatal pigs (n=6) and preadipocytes induced to differentiate in vitro for 8 days in the presence of insulin, hydrocortisone, and rosiglitazone. Total RNA was extracted from these cultures on days 0 and 8 post-induction. Real-time PCR was then utilized to determine changes in mRNA expression for collagen type I alpha 1 chain (COL1A), collagen type I alpha 2 chain (COL2A), collagen type I alpha 3 chain (COL3A), collagen type I alpha 4 chain (COL4A), collagen type I alpha 6 chain (COL6A), biglycan, fibronectin, laminin, nitogen-1 (NID1), matrix metallopeptidase 2 (MMP2), matrix metallopeptidase 9 (MMP9), metallopeptidase inhibitor 3 (TIMP3). The mRNA abundances of COL1A, COL3A and MMP2 were significantly downregulated 2.86-fold (P < 0.05), 16.7-fold (P < 0.01) and 3.1-fold (P < 0.05) respectively in day 8 (differentiated) compared to day 0 (undifferentiated) cultures. Meanwhile, mRNA abundances were significantly upregulated during adipogenesis for the COL2A (2.82-fold; P < 0.05), COL4A (2.01-fold; P < 0.05), COL6A (2.8-fold; P < 0.05), biglycan (49.9- fold; P < 0.001), fibronectin (452-fold; P < 0.001), laminin (6.1-fold; P < 0.05), NID1(47.4-fold; P < 0.01), MMP9 (76.8- fold; P < 0.01), and TIMP3(3.04-fold; P < 0.05) genes. These data support the hypothesis that significant changes in ECM components occur during porcine adipogenesis. Modulating adipose tissue ECM remodeling might be a novel strategy to manipulate adiposity in the pig.

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