scholarly journals Simulating intervertebral disc cell behavior within 3D multifactorial environments

2019 ◽  
Author(s):  
L. Baumgartner ◽  
J.J. Reagh ◽  
M.A. González Ballester ◽  
J. Noailly
Keyword(s):  
Experimental Data ◽  
Intervertebral Disc ◽  
Cell Viability ◽  
Mrna Expression ◽  
Type I Collagen ◽  
Collagen Type ◽  
Cell Behavior ◽  
Type I ◽  
Nucleus Pulposus Cells ◽  
Model Predictions

AbstractMotivationLow back pain is responsible for more global disability than any other condition. Its incidence is closely related to intervertebral disc (IVD) failure, which is likely caused by an accumulation of microtrauma within the IVD. Crucial factors in microtrauma development are not entirely known yet, probably because their exploration in vivo or in vitro remains tremendously challenging. In-silico modelling is, therefore, definitively appealing, and shall include approaches to integrate influences of multiple cell stimuli at the microscale. Accordingly, this study introduces a hybrid Agent-based (AB) model in IVD research and exploits network modelling solutions in systems biology to mimic the cellular behavior of Nucleus Pulposus cells exposed to a 3D multifactorial biochemical environment, based on mathematical integrations of existing experimental knowledge. Cellular activity reflected by mRNA expression of Aggrecan, Collagen type I, Collagen type II, MMP-3 and ADAMTS were calculated for inflamed and non-inflamed cells. mRNA expression over long periods of time is additionally determined including cell viability estimations. Model predictions were eventually validated with independent experimental data.ResultsAs it combines experimental data to simulate cell behavior exposed to a multifactorial environment, the present methodology was able to reproduce cell death within 3 days under glucose deprivation and a 50% decrease in cell viability after 7 days in an acidic environment. Cellular mRNA expression under non-inflamed conditions simulated a quantifiable catabolic shift under an adverse cell environment, and model predictions of mRNA expression of inflamed cells provide new explanation possibilities for unexpected results achieved in experimental [email protected]

scholarly journals Simulating intervertebral disc cell behaviour within 3D multifactorial environments

2020 ◽  
Author(s):  
L Baumgartner ◽  
J J Reagh ◽  
M A González Ballester ◽  
J Noailly
Keyword(s):  
Experimental Data ◽  
Intervertebral Disc ◽  
Cell Viability ◽  
Mrna Expression ◽  
Collagen Type ◽  
Supplementary Information ◽  
Model Parameters ◽  
Type I ◽  
Cell Behaviour ◽  
Model Predictions

Abstract Motivation Low back pain is responsible for more global disability than any other condition. Its incidence is closely related to intervertebral disc (IVD) failure, which is likely caused by an accumulation of microtrauma within the IVD. Crucial factors in microtrauma development are not entirely known yet, probably because their exploration in vivo or in vitro remains tremendously challenging. In silico modelling is, therefore, definitively appealing, and shall include approaches to integrate influences of multiple cell stimuli at the microscale. Accordingly, this study introduces a hybrid Agent-based (AB) model in IVD research and exploits network modelling solutions in systems biology to mimic the cellular behaviour of Nucleus Pulposus cells exposed to a 3D multifactorial biochemical environment, based on mathematical integrations of existing experimental knowledge. Cellular activity reflected by mRNA expression of Aggrecan, Collagen type I, Collagen type II, MMP-3 and ADAMTS were calculated for inflamed and non-inflamed cells. mRNA expression over long periods of time is additionally determined including cell viability estimations. Model predictions were eventually validated with independent experimental data. Results As it combines experimental data to simulate cell behaviour exposed to a multifactorial environment, the present methodology was able to reproduce cell death within 3 days under glucose deprivation and a 50% decrease in cell viability after 7 days in an acidic environment. Cellular mRNA expression under non-inflamed conditions simulated a quantifiable catabolic shift under an adverse cell environment, and model predictions of mRNA expression of inflamed cells provide new explanation possibilities for unexpected results achieved in experimental research. Availabilityand implementation The AB model as well as used mathematical functions were built with open source software. Final functions implemented in the AB model and complete AB model parameters are provided as Supplementary Material. Experimental input and validation data were provided through referenced, published papers. The code corresponding to the model can be shared upon request and shall be reused after proper training. Contact [email protected] Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Effect of acute resistance exercise and sex on human patellar tendon structural and regulatory mRNA expression

2009 ◽  
Vol 106 (2) ◽  
pp. 468-475 ◽  
Author(s):  
Bridget E. Sullivan ◽  
Chad C. Carroll ◽  
Bozena Jemiolo ◽  
Scott W. Trappe ◽  
S. Peter Magnusson ◽  
...  
Keyword(s):  
Resistance Exercise ◽  
Mrna Expression ◽  
Patellar Tendon ◽  
Type I Collagen ◽  
Collagen Type ◽  
Collagen Type I ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Type I ◽  
Collagen Type Iii ◽  
Type Iii

Tendon is mainly composed of collagen and an aqueous matrix of proteoglycans that are regulated by enzymes called matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Although it is known that resistance exercise (RE) and sex influence tendon metabolism and mechanical properties, it is uncertain what structural and regulatory components contribute to these responses. We measured the mRNA expression of tendon's main fibrillar collagens (type I and type III) and the main proteoglycans (decorin, biglycan, fibromodulin, and versican) and the regulatory enzymes MMP-2, MMP-9, MMP-3, and TIMP-1 at rest and after RE. Patellar tendon biopsy samples were taken from six individuals (3 men and 3 women) before and 4 h after a bout of RE and from a another six individuals (3 men and 3 women) before and 24 h after RE. Resting mRNA expression was used for sex comparisons (6 men and 6 women). Collagen type I, collagen type III, and MMP-2 were downregulated ( P < 0.05) 4 h after RE but were unchanged ( P > 0.05) 24 h after RE. All other genes remained unchanged ( P > 0.05) after RE. Women had higher resting mRNA expression ( P < 0.05) of collagen type III and a trend ( P = 0.08) toward lower resting expression of MMP-3 than men. All other genes were not influenced ( P > 0.05) by sex. Acute RE appears to stimulate a change in collagen type I, collagen type III, and MMP-2 gene regulation in the human patellar tendon. Sex influences the structural and regulatory mRNA expression of tendon.

scholarly journals Investigation of intervertebral disc degeneration using multivariate FTIR spectroscopic imaging

2016 ◽  
Vol 187 ◽  
pp. 393-414 ◽  
Author(s):  
Kerstin T. Mader ◽  
Mirte Peeters ◽  
Suzanne E. L. Detiger ◽  
Marco N. Helder ◽  
Theo H. Smit ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Type I Collagen ◽  
Collagen Type ◽  
Collagen Type I ◽  
Quantitative Information ◽  
Multivariate Curve Resolution ◽  
Type I ◽  
Tissue Samples ◽  
Immunohistochemical Stains

Traditionally tissue samples are analysed using protein or enzyme specific stains on serial sections to build up a picture of the distribution of components contained within them. In this study we investigated the potential of multivariate curve resolution-alternating least squares (MCR-ALS) to deconvolute 2nd derivative spectra of Fourier transform infrared (FTIR) microscopic images measured in transflectance mode of goat and human paraffin embedded intervertebral disc (IVD) tissue sections, to see if this methodology can provide analogous information to that provided by immunohistochemical stains and bioassays but from a single section. MCR-ALS analysis of non-degenerate and enzymatically in vivo degenerated goat IVDs reveals five matrix components displaying distribution maps matching histological stains for collagen, elastin and proteoglycan (PG), as well as immunohistochemical stains for collagen type I and II. Interestingly, two components exhibiting characteristic spectral and distribution profiles of proteoglycans were found, and relative component/tissue maps of these components (labelled PG1 and PG2) showed distinct distributions in non-degenerate versus mildly degenerate goat samples. MCR-ALS analysis of human IVD sections resulted in comparable spectral profiles to those observed in the goat samples, highlighting the inter species transferability of the presented methodology. Multivariate FTIR image analysis of a set of 43 goat IVD sections allowed the extraction of semi-quantitative information from component/tissue gradients taken across the IVD width of collagen type I, collagen type II, PG1 and PG2. Regional component/tissue parameters were calculated and significant correlations were found between histological grades of degeneration and PG parameters (PG1: p = 0.0003, PG2: p < 0.0001); glycosaminoglycan (GAG) content and PGs (PG1: p = 0.0055, PG2: p = 0.0001); and MRI T2* measurements and PGs (PG1: p = 0.0021, PG2: p < 0.0001). Additionally, component/tissue parameters for collagen type I and II showed significant correlations with total collagen content (p = 0.0204, p = 0.0127). In conclusion, the presented findings illustrate, that the described multivariate FTIR imaging approach affords the necessary chemical specificity to be considered an important tool in the study of IVD degeneration in goat and human IVDs.

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 &lt; 0.05), 16.7-fold (P &lt; 0.01) and 3.1-fold (P &lt; 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 &lt; 0.05), COL4A (2.01-fold; P &lt; 0.05), COL6A (2.8-fold; P &lt; 0.05), biglycan (49.9- fold; P &lt; 0.001), fibronectin (452-fold; P &lt; 0.001), laminin (6.1-fold; P &lt; 0.05), NID1(47.4-fold; P &lt; 0.01), MMP9 (76.8- fold; P &lt; 0.01), and TIMP3(3.04-fold; P &lt; 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.

scholarly journals Genetic and physiological variation in two strains of Japanese quail

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Nashat Saeid Ibrahim ◽  
Mohammed Ahmed El-Sayed ◽  
Heba Abdelwahab Mahmoud Assi ◽  
Ahmed Enab ◽  
Abdel-Moneim Eid Abdel-Moneim
Keyword(s):  
Japanese Quail ◽  
Type I Collagen ◽  
Collagen Type ◽  
Pectoral Muscle ◽  
Collagen Type I ◽  
Scientific Basis ◽  
Type I ◽  
Improvement Program ◽  
Body Weights ◽  
Physiological Variations

Abstract Background Detecting the genetic and physiological variations in two Japanese quail strains could be used to suggest a new avian model for future breeding studies. Consequently, two estimations were performed on two Japanese quail strains: gray quail strain (GJQS) and white jumbo quail strain (WJQS). The first estimation was conducted on carcass characteristics, breast muscles, breast concentration of collagen type I, and body measurements. In contrast, blood samples were collected for the second estimation for genomic DNA extraction and genetic analysis. Results A total of 62 alleles out of 97 specific alleles (63.92%) were detected overall loci (14 microsatellite loci) for the two strains. A total of 27 specific alleles of WJQS were observed, and 35 were obtained for GJQS. The percentage of similarity was 48.09% ranged from 4.35 with UBC001 to 100% with GUJ0051. WJQS had greater body weights and a higher value of pectoral muscle and supracoracoideus muscle than GJQS. The breast muscles of GJQS exhibited a higher concentration of type I collagen than the WJQS. Furthermore, males showed higher concentrations of collagen type I than females. WJQS showed a higher body length, chest girth, chest length, thigh length, thigh girth, drumstick length, and drumstick girth (cm) than GJQS. WJQS showed more significant differences in carcass traits compared with GJQS. Conclusion The physiological differences between WJQS and GJQS were ascertained with microsatellite markers, which indicated high polymorphism between these strains. These observations provided a scientific basis for evaluating and utilizing the genetic resources of WJQS and GJQS in a future genetic improvement program.

scholarly journals Transcriptomics Study to Determine the Molecular Mechanism by which sIL-13Rα2-Fc Inhibits Caudal Intervertebral Disc Degeneration in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xin Wang ◽  
Jianshi Tan ◽  
Junhao Sun ◽  
Pengzhong Fang ◽  
Jinlei Chen ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Type I Collagen ◽  
Type Ii Collagen ◽  
Type I ◽  
Model Group ◽  
Expression Levels ◽  
Protein Levels ◽  
Collagen Protein

Background. Intervertebral disc degeneration is related to tissue fibrosis. ADAMTS can degrade the important components of the ECM during the process of intervertebral disc degeneration, ultimately resulting in the loss of intervertebral disc function. sIL-13Rα2-Fc can inhibit fibrosis and slow down the degeneration process, but the mechanism involved remains unclear. Objective. To determine the mechanism by which sIL-13Rα2-Fc inhibits ECM degradation and reduces intervertebral disc tissue fibrosis using a transcriptomics analysis. Methods. A rat model of caudal intervertebral disc degeneration was established, and Sirius red staining was used to observe the pathological changes in the caudal intervertebral disc. Transcriptome sequencing was employed to assess the gene expression profiles of the intervertebral disc tissues in the model group and the sIL-13Rα2-Fc-treated group. Differentially expressed genes were identified and analyzed using GO annotation and KEGG pathway analyses. Real-time fluorescence quantitative PCR was used to verify the expression levels of candidate genes. The levels of GAG and HA were quantitatively assessed by ELISA, and the levels of collagen I and collagen II were analyzed by western blotting. Results. Sirius red staining showed that in the model group, the annulus fibrosus was disordered, the number of breaks increased, and the type I collagen protein levels increased, whereas in the sIL-13Rα2-Fc group, the annulus fibrosus was ordered, the number of breaks decreased, and the type II collagen protein levels increased. In comparison with the model group, we identified 58 differentially expressed genes in the sIL-13Rα2-Fc group, and these were involved in 35 signaling pathways. Compared with those in the model group, the mRNA expression levels of Rnux1, Sod2, and Tnfaip6 in the IL-13Rα2-Fc group were upregulated, and the mRNA expression levels of Aldh3a1, Galnt3, Fgf1, Celsr1, and Adamts8 were downregulated; these results were verified by real-time fluorescence quantitative PCR. TIMP-1 (an ADAMTS inhibitor) and TIMP-1 combined with the sIL-13Rα2-Fc intervention increased the levels of GAG and HA, inhibited the expression of type I collagen, and promoted the expression of type II collagen. Conclusion. Adamts8 may participate in the degradation of ECM components such as GAG and HA and lead to an imbalance in the ECM of the intervertebral disc, resulting in intervertebral disc degeneration. sIL-13Rα2-Fc promoted anabolism of the ECM and increased the levels of ECM components by inhibiting the expression of Adamts8, thus maintaining the dynamic equilibrium of the ECM and ultimately delaying intervertebral disc degeneration.

Electromagnetic fields enhance chondrogenesis of human adipose-derived stem cells in a chondrogenic microenvironment in vitro

2013 ◽  
Vol 114 (5) ◽  
pp. 647-655 ◽  
Author(s):  
Chung-Hwan Chen ◽  
Yi-Shan Lin ◽  
Yin-Chih Fu ◽  
Chih-Kuang Wang ◽  
Shun-Cheng Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Electromagnetic Field ◽  
Cell Viability ◽  
Chondrogenic Differentiation ◽  
Collagen Type ◽  
Cartilage Tissue ◽  
Pulse Electromagnetic Field ◽  
Type I ◽  
Adipose Derived Stem Cells ◽  
Pemf Treatment

We tested the hypothesis that electromagnetic field (EMF) stimulation enhances chondrogenesis in human adipose-derived stem cells (ADSCs) in a chondrogenic microenvironment. A two-dimensional hyaluronan (HA)-coated well (2D-HA) and a three-dimensional pellet culture system (3D-pellet) were used as chondrogenic microenvironments. The ADSCs were cultured in 2D-HA or 3D-pellet, and then treated with clinical-use pulse electromagnetic field (PEMF) or the innovative single-pulse electromagnetic field (SPEMF) stimulation. The cytotoxicity, cell viability, and chondrogenic and osteogenic differentiations were analyzed after PEMF or SPEMF treatment. The modules of PEMF and SPEMF stimulations used in this study did not cause cytotoxicity or alter cell viability in ADSCs. Both PEMF and SPEMF enhanced the chondrogenic gene expression (SOX-9, collagen type II, and aggrecan) of ADSCs cultured in 2D-HA and 3D-pellet. The expressions of bone matrix genes (osteocalcin and collagen type I) of ADSCs were not changed after SPEMF treatment in 2D-HA and 3D-pellet; however, they were enhanced by PEMF treatment. Both PEMF and SPEMF increased the cartilaginous matrix (sulfated glycosaminoglycan) deposition of ADSCs. However, PEMF treatment also increased mineralization of ADSCs, but SPEMF treatment did not. Both PEMF and SPEMF enhanced chondrogenic differentiation of ADSCs cultured in a chondrogenic microenvironment. SPEMF treatment enhanced ADSC chondrogenesis, but not osteogenesis, when the cells were cultured in a chondrogenic microenvironment. However, PEMF enhanced both osteogenesis and chondrogenesis under the same conditions. Thus the combination of a chondrogenic microenvironment with SPEMF stimulation can promote chondrogenic differentiation of ADSCs and may be applicable to articular cartilage tissue engineering.

scholarly journals SAT0298 IS INTERLEUKIN 6 A FACTOR OF FIBROGENESIS IN DERMAL FIBROBLASTS?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1094.1-1094
Author(s):  
A. S. Siebuhr ◽  
P. Juhl ◽  
M. Karsdal ◽  
A. C. Bay-Jensen
Keyword(s):  
Gene Expression ◽  
Type I Collagen ◽  
Collagen Type ◽  
Collagen Type I ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Dependent Manner ◽  
Full Time ◽  
Collagen Formation ◽  
Type Iii

Background:Interleukin 6 (IL-6) is known to have both pro- and anti-inflammatory properties, depending on the receptor activation. The classical IL-6 signaling via the membrane bound receptor is mainly anti-inflammatory, whereas signaling through the soluble receptor (sIL-6R) is pro-inflammatory/pro-fibrotic. However, the direct fibrotic effect of IL-6 stimulation on dermal fibroblasts is unknown.Objectives:We investigated the fibrotic effect of IL-6 + sIL-6R in a dermal fibroblast model and assessed fibrosis by neo-epitope biomarkers of extracellular matrix proteins.Methods:Primary healthy human dermal fibroblasts were grown for up to 17 days in DMEM medium with 0.4% fetal calf serum, ficoll (to produce a crowded environment) and ascorbic acid. IL-6 [1-90 nM]+sIL-6R [0.1-9 nM] alone or in combination with TGFβ [1 nM] were tested in three different donors. TGFβ [1 nM], PDGF-AB [3 nM] and non-stimulated cells (w/o) were used as controls. Tocilizumab (TCZ) with TGFβ + IL-6 + sIL-6R stimulation was tested in one donor. Collagen type I, III and VI formation (PRO-C1, PRO-C3 and PRO-C6) and fibronectin (FBN-C) were evaluated by validated ELISAs (Nordic Bioscience). Western blot analysis investigated signal cascades. Gene expression of selected ECM proteins was analyzed. Statistical analyses included One-way and 2-way ANOVA and area under the curve analysis.Results:formation by the end of the culture period. The fibronectin and collagen type VI signal were consistent between the three tested donors, whereas the formation of type III collagen was only increased in one donor, but in several trials. Type I collagen formation was unchanged by IL-6 + sIL-6R stimulation. The gene expression of type I collagen was induced by IL-6 + sIL-6R. Western blot analysis validated trans-signaling by the IL-6+sIL-6R stimulation as expected.IL-6 + sIL-6R stimulation in combination with TGFβ decreased fibronectin levels compared to TGFβ alone but did not reach the level of unstimulated fibroblasts. The formation of collagen type IV was generally unchanged with IL-6 + sIL-6R + TGFβ compared to TGFβ alone. Collagen type I and III formation was more scattered in the signals when IL-6 + sIL-6R was in combination with TGFβ, as the biomarker level could be either decreased or increased compared to TGFβ alone. In two studies the type I collagen level was synergistic increased by IL-6 + sIL-6R + TGFβ, whereas another study found the level to be decreased compared to TGFβ alone. The gene expression of fibronectin and type I collagen was increased with TGFβ +IL-6+sIL-6R compared to TGFβ alone.Inhibition of IL-6R by TCZ in combination with IL-6 + sIL-6R did only decrease the fibronectin level with the lowest TCZ concentration (p=0.03). TCZ alone decreased the fibronectin level in a dose-dependent manner (One-way ANOVA p=0.0002).Conclusion:We investigated the fibrotic response of dermal fibroblasts to IL-6 + sIL-6R stimulation. IL-6 modulated the fibronectin level and modulated the collagen type III formation level in a somewhat dose-dependent manner. In combination with TGFβ, IL-6 decreased collagen type I and IV formation and fibronectin. However, in this study inhibition of IL-6R by TCZ did not change the fibrotic response of the dermal fibroblasts. This study indicated that IL-6 did not induce collagen formation in dermal fibroblasts, except type III collagen formation with high IL-6 concentration.Figure:Disclosure of Interests:Anne Sofie Siebuhr Employee of: Nordic Bioscience, Pernille Juhl Employee of: Nordic Bioscience, Morten Karsdal Shareholder of: Nordic Bioscience A/S., Employee of: Full time employee at Nordic Bioscience A/S., Anne-Christine Bay-Jensen Shareholder of: Nordic Bioscience A/S, Employee of: Full time employee at Nordic Bioscience A/S.

scholarly journals Endothelial cell growth factor and heparin regulate collagen gene expression in keloid fibroblasts

1991 ◽  
Vol 278 (3) ◽  
pp. 863-869 ◽  
Author(s):  
E M L Tan ◽  
J Peltonen
Keyword(s):  
Gene Expression ◽  
Endothelial Cell ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Collagen Type ◽  
Collagen Type I ◽  
Type I ◽  
Collagen Gene ◽  
Endothelial Cell Growth Factor ◽  
Endothelial Cell Growth

Keloids are benign cutaneous tumours characterized by excess deposition of collagen, specifically type I collagen. We report here that collagen biosynthesis, as measured by hydroxyproline synthesis, was markedly inhibited by 65-80% by the combination of endothelial cell growth factor (ECGF) supplement and heparin in keloid fibroblast cultures. Fibroblast cultures that were incubated with ECGF alone also demonstrated a measurable decrease of approx. 50% in collagen synthesis compared with control cultures. The inhibition of collagen synthesis was related to the down-regulation of collagen gene expression. Quantitative measurements of mRNA-cDNA hybrids revealed that the gene expression of collagen type I was decreased by more than 80% by heparin and ECGF. Markedly diminished levels of mRNA encoding collagen type I were also observed in cultures incubated with ECGF alone. The results show that ECGF and heparin elicit a negative regulatory effect on collagen production, and that this inhibition is due largely to the down-regulation of the pro-alpha 1(I) of type I collagen gene. Furthermore, ECGF has a potent suppressive effect, and heparin provides an additive effect to this inhibitory phenomenon.

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