Role of TGF-β1 in relation to exercise-induced type I collagen synthesis in human tendinous tissue

2003 ◽  
Vol 95 (6) ◽  
pp. 2390-2397 ◽  
Author(s):  
Katja Heinemeier ◽  
Henning Langberg ◽  
Jens L. Olesen ◽  
Michael Kjaer
Keyword(s):  
Mechanical Loading ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Plasma Concentrations ◽  
Treadmill Running ◽  
Blood Levels ◽  
Type I ◽  
Response To Exercise

Mechanical loading of tissue is known to influence local collagen synthesis, and microdialysis studies indicate that mechanical loading of human tendon during exercise elevates tendinous type I collagen production. Transforming growth factor-β1 (TGF-β1), a potent stimulator of type I collagen synthesis, is released from cultured tendon fibroblasts in response to mechanical loading. Thus TGF-β1 could link mechanical loading and collagen synthesis in tendon tissue in vivo. Tissue levels of TGF-β1 and type I collagen metabolism markers [procollagen I COOH-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen (ICTP)] were measured by microdialysis in peritendinous tissue of the Achilles' tendon in six male volunteers before and after treadmill running (1 h, 12 km/h, 3% uphill). In addition, blood levels of TGF-β1, PICP, and ICTP were obtained. PICP levels increased 68 h after exercise ( P < 0.05). Dialysate levels of TGF-β1 changed from 303 ± 46 pg/ml (at rest) to 423 ± 86 pg/ml 3 h postexercise. This change was nonsignificant, but the decay of tissue TGF-β1 after catheter insertion was markedly delayed by exercise compared with the decay seen in resting subjects. Plasma concentrations of TGF-β1 rose 30% in response to exercise ( P < 0.05 vs. pre). Our observations indicate an increased local production of type I collagen in human peritendinous tissue in response to uphill running. Although not conclusive, changes in circulating and local TGF-β1, in response to exercise, suggest a role for TGF-β1 in mechanical regulation of local collagen type I synthesis in tendon-related connective tissue in vivo.

scholarly journals High doses of TGF-β potently suppress type I collagen via the transcription factor CUX1

2011 ◽  
Vol 22 (11) ◽  
pp. 1836-1844 ◽  
Author(s):  
Maria Fragiadaki ◽  
Tetsurou Ikeda ◽  
Abigail Witherden ◽  
Roger M Mason ◽  
David Abraham ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Transforming Growth Factor Β ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Aberrant Expression

Transforming growth factor-β (TGF-β) is an inducer of type I collagen, and uncontrolled collagen production leads to tissue scarring and organ failure. Here we hypothesize that uncovering a molecular mechanism that enables us to switch off type I collagen may prove beneficial in treating fibrosis. For the first time, to our knowledge, we provide evidence that CUX1 acts as a negative regulator of TGF-β and potent inhibitor of type I collagen transcription. We show that CUX1, a CCAAT displacement protein, is associated with reduced expression of type I collagen both in vivo and in vitro. We show that enhancing the expression of CUX1 results in effective suppression of type I collagen. We demonstrate that the mechanism by which CUX1 suppresses type I collagen is through interfering with gene transcription. In addition, using an in vivo murine model of aristolochic acid (AA)-induced interstitial fibrosis and human AA nephropathy, we observe that CUX1 expression was significantly reduced in fibrotic tissue when compared to control samples. Moreover, silencing of CUX1 in fibroblasts from kidneys of patients with renal fibrosis resulted in increased type I collagen expression. Furthermore, the abnormal CUX1 expression was restored by addition of TGF-β via the p38 mitogen-activated protein kinase pathway. Collectively, our study demonstrates that modifications of CUX1 expression lead to aberrant expression of type I collagen, which may provide a molecular basis for fibrogenesis.

scholarly journals The Effectiveness of Depigmentation, Interleukin-1B, and Transforming Growth Factor-B Antibodies in Activating and Increasing Collagenase in Keloid as Adjuvant Therapy After Scar Excision

2021 ◽  
Vol 2 (1) ◽  
pp. 16-22
Author(s):  
Savira Butsainah Dienanta ◽  
Ayik Rochyatul Jannah ◽  
Faiza Rahma Ebnudesita ◽  
Reny I'tishom
Keyword(s):  
Growth Factor ◽  
Adjuvant Therapy ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Target Location ◽  
Drug Carrier ◽  
Healing Process ◽  
Wound Healing Process ◽  
Type I

Background: Keloid is an abnormal scar in previously traumatic skin after going through the wound healing process. One hundred million cases have been found in developing countries with the main complaint of scar appearances. To overcome this problem, 24 literatures from various journals and textbooks are reviewed. Reviews: Keloid formation is based on high melanin amount which inhibits the collagenase enzyme. Moreover, the high melanin amount would block interleukin (IL)-1B work resulting in collagen synthesis and collagenase reduction. Depigmentation effort with 4% hydroquinone is implemented to reduce the amount of melanin presented in the skin. With melanin reduction, IL-1B can work optimally by inhibiting fibroblast growth in keloid tissue without affecting on normal skin. It also induces Matrix Metalloproteinase (MMP)-1 which is an interstitial collagenase. IL-1B has an opposing effect compared to Transforming Growth Factor (TGF)-B, thus TGF-B antibody is needed to potentiate IL-1B therapeutic effect. TGF-B antibody can neutralize TGF-B ligand and avB6 integrin resulting in blocking of COL1A1 gene expression which is responsible for MMP-1 production and type-I collagen synthesis. These three components are combined in cream with liposome as a drug carrier. This combination is applicated for adjuvant therapy after scar excision. Liposomes are chosen because of their high biocompatibility, low toxicity, and low biodegradability. Liposomes also can release slowly in the extravascular area such as skin. This advantage may carry drug components effectively to the target location. Summary: The combination of depigmentation, IL-1B, and TGF-B antibodies has a potency to be developed as a future adjuvant therapy of keloid.

scholarly journals Dioscin alleviates alcoholic liver fibrosis by attenuating hepatic stellate cell activation via the TLR4/MyD88/NF-κB signaling pathway

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Min Liu ◽  
Youwei Xu ◽  
Xu Han ◽  
Lianhong Yin ◽  
Lina Xu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Signaling Pathway ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Stellate Cell ◽  
Pyrrolidine Dithiocarbamate ◽  
Type I ◽  
Tgf Β1

Abstract The present work aimed to investigate the activities and underlying mechanisms of dioscin against alcoholic liver fibrosis (ALF). In vivo liver fibrosis in mice was induced by an alcoholic liquid diet and in vitro studies were performed on activated HSC-T6 and LX2 cells treated with lipopolysaccharide. Our results showed that dioscin significantly attenuated hepatic stellate cells (HSCs) activation, improved collagen accumulation and attenuated inflammation through down-regulating the levels of myeloid differentiation factor 88 (MyD88), nuclear factor κB (NF-κB), interleukin (IL)-1, IL-6 and tumour necrosis factor-α by decreasing Toll-like receptor (TLR)4 expression both in vivo and in vitro. TLR4 overexpression was also decreased by dioscin, leading to the markedly down-regulated levels of MyD88, NF-κB, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA) and type I collagen (COL1A1) in cultured HSCs. Suppression of cellular MyD88 by ST2825 or abrogation of NF-κB by pyrrolidine dithiocarbamate eliminated the inhibitory effects of dioscin on the levels of TGF-β1, α-SMA and COL1A1. In a word, dioscin exhibited potent effects against ALF via altering TLR4/MyD88/NF-κB signaling pathway, which provided novel insights into the mechanisms of this compound as an antifibrogenic candidate for the treatment of ALF in the future.

Sequential extracts of human bone show differing collagen synthetic rates

2002 ◽  
Vol 30 (2) ◽  
pp. 61-65 ◽  
Author(s):  
J. Babraj ◽  
D.J. Cuthbertson ◽  
P. Rickhuss ◽  
W. Meier-Augenstein ◽  
K. Smith ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Human Bone ◽  
Bone Collagen ◽  
Type I ◽  
Human Beings ◽  
Collagen Turnover ◽  
Bone Collagen Synthesis

Type I collagen is the major bone protein. Little is known quantitatively about human bone collagen synthesis in vivo, despite its importance for the understanding of bone formation and turnover. Our aim was to develop a method that could be used for the physiological and pathophysiological investigation of human bone collagen synthesis. We have carried out preliminary studies in patients undergoing hip replacement and in pigs to validate the use of the flooding dose method using 13C- or 15N-labelled proline and we have now refined our techniques to allow them to be used in a normal clinical or physiological setting. The results show that the application of a flooding dose causes bone free-proline labelling to equilibrate with that of blood in pigs and human beings, so that only 150 mg of bone will provide enough sample to prepare and measure the labelling of three fractions of bone collagen (dissolved in NaCl, acetic acid and pepsin/acetic acid) which have the same relative labelling (1.0:0.43:0.1) as measured by GC-combustion-isotope ratio MS. The rates of incorporation were substantially faster than in skeletal muscle samples taken at the same time. The results suggest that different fractions of human bone collagen turnover at markedly higher rates than had been previously considered. This approach should allow us to discover how growth and development, food, activity and drugs affect bone collagen turnover and to measure the effects on it of ageing and bone disease.

scholarly journals Biochemical role of the collagen-rich tumour microenvironment in pancreatic cancer progression

2011 ◽  
Vol 441 (2) ◽  
pp. 541-552 ◽  
Author(s):  
Mario A. Shields ◽  
Surabhi Dangi-Garimella ◽  
Amanda J. Redig ◽  
Hidayatullah G. Munshi
Keyword(s):  
Extracellular Matrix ◽  
Cancer Progression ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Ductal Adenocarcinoma ◽  
Type I ◽  
Desmoplastic Reaction ◽  
Tgf Β1

PDAC (pancreatic ductal adenocarcinoma) is among the most deadly of human malignances. A hallmark of the disease is a pronounced collagen-rich fibrotic extracellular matrix known as the desmoplastic reaction. Intriguingly, it is precisely these areas of fibrosis in which human PDAC tumours demonstrate increased expression of a key collagenase, MT1-MMP [membrane-type 1 MMP (matrix metalloproteinase); also known as MMP-14]. Furthermore, a cytokine known to mediate fibrosis in vivo, TGF-β1 (transforming growth factor-β1), is up-regulated in human PDAC tumours and can promote MT1-MMP expression. In the present review, we examine the regulation of PDAC progression through the interplay between type I collagen (the most common extracellular matrix present in human PDAC tumours), MT1-MMP and TGF-β1. Specifically, we examine the way in which signalling events through these pathways mediates invasion, regulates microRNAs and contributes to chemoresistance.

Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women

2009 ◽  
Vol 106 (4) ◽  
pp. 1435-1443 ◽  
Author(s):  
M. Hansen ◽  
B. F. Miller ◽  
L. Holm ◽  
S. Doessing ◽  
S. G. Petersen ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Patellar Tendon ◽  
Oral Contraceptives ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Vastus Lateralis ◽  
Type I ◽  
High Concentration ◽  
Igf I

Women are at greater risk than men for certain kinds of diseases and injuries, which may at least partly be caused by sex hormonal differences. We aimed to test the influence of estradiol in vivo on collagen synthesis in tendon, bone, and muscle. Two groups of young, healthy women similar in age, body composition, and exercise-training status were included. The two groups were either habitual users of oral contraceptives exposed to a high concentration of synthetic estradiol and progestogens (OC, n = 11), or non-OC-users tested in the follicular phase of the menstrual cycle characterized by low concentrations of estradiol and progesterone (control, n = 12). Subjects performed 1 h of one-legged kicking exercise. The next day collagen fractional synthesis rates (FSR) in tendon and muscle connective tissue were measured after a flooding dose of [13C]proline followed by biopsies from the patellar tendon and vastus lateralis in both legs. Simultaneously, microdialysis catheters were inserted in vastus lateralis and in front of the patellar tendon for measurement of insulin-like growth factor I (IGF-I) and its binding proteins. Serum NH2-terminal propeptide of type I collagen (PINP) and urine COOH-terminal telopeptides of type-I collagen (CTX-I) were measured as markers for bone synthesis and breakdown, respectively. Tendon FSR and PINP were lower in OC compared with control. An increase in muscle collagen FSR postexercise was only observed in control ( P < 0.05). Furthermore, the results indicate a lower bioavailability of IGF-I in OC. In conclusion, synthetic female sex hormones administered as OC had an inhibiting effect on collagen synthesis in tendon, bone, and muscle connective tissue, which may be related to a lower bioavailability of IGF-I.

Exercise-dependent IGF-I, IGFBPs, and type I collagen changes in human peritendinous connective tissue determined by microdialysis

2007 ◽  
Vol 102 (1) ◽  
pp. 214-220 ◽  
Author(s):  
Jens L. Olesen ◽  
Katja M. Heinemeier ◽  
Carsten Gemmer ◽  
Michael Kjær ◽  
Allan Flyvbjerg ◽  
...  
Keyword(s):  
Mechanical Loading ◽  
Collagen Synthesis ◽  
Acute Exercise ◽  
Type I Collagen ◽  
Exercise Group ◽  
Control Group ◽  
Local Concentration ◽  
Type I ◽  
Collagen Production ◽  
Igf I

Microdialysis studies indicate that mechanical loading of human tendon during exercise elevates type I collagen production in tendon. However, the possibility that the insertion of microdialysis fibers per se may increase the local collagen production due to trauma has not been explored. Insulin-like growth factor I (IGF-I) and its binding proteins (IGFBPs), which are known to stimulate collagen production in animal tendons, may regulate the translation of mechanical loading to collagen synthesis. Systemic and tissue levels of IGF-I, IGFBP, and type I collagen metabolism markers [procollagen I COOH-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen] were measured by microdialysis in peritendinous tissue of the human Achilles tendon in an exercise group (performing a 36-km run, n = 6) and a control group (no intervention, n = 6). An increase in local PICP concentration was seen in both groups after 72 h and stayed elevated in the exercise group at 96 h ( P < 0.05). IGFBP-1 in both serum and dialysate increased in the exercise group immediately after exercise ( P < 0.05), whereas IGFBP-3 decreased systemically ( P < 0.05). Elevation of local IGFBP-4 was observed in both the control and exercise groups after 48 h ( P < 0.05). Total IGF-I did not change in locally or systemically in either group. Our results indicate an increased local production of PICP in human peritendinous tissue in response to prolonged mechanical loading with part of the increase due to trauma from the sampling technique. Care must therefore be emphasized to minimize the numbers of insertions with microdialysis. We demonstrated an elevation of IGFBP-1 both systemically and peritendinously in response to prolonged acute exercise. The local increased collagen synthesis was preceded by an elevation of local concentration of IGFBP-4, suggesting that IGFBP-4 may have a key role in the IGF-axis effect on the human collagen synthesis in vivo.

scholarly journals Rates of collagen synthesis in lung, skin and muscle obtained in vivo by a simplified method using [3H]proline

1982 ◽  
Vol 206 (3) ◽  
pp. 535-544 ◽  
Author(s):  
G J Laurent
Keyword(s):  
Large Dose ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Specific Radioactivity ◽  
Extracellular Proteins ◽  
Type I ◽  
Body Tissues ◽  
Collagen Protein ◽  
Simplified Method

Methods for measurement of rates of collagen synthesis in vivo have thus far been technically difficult and often subject to quite large errors. In this paper a simplified method is described for obtaining synthesis rates of collagen and non-collagen proteins, for tissues of rabbits. This involves an intravenous injection of [3H]proline, administered with a large dose of unlabelled proline, and measurement of the specific radioactivity of proline and hydroxyproline in body tissues up to 3 h later. The specific radioactivity of [3H]proline in plasma and the tissue free pools rises rapidly to a plateau value which is maintained for at least 2 h, when the specific radioactivity of the type I collagen precursors, isolated from the skin, was similar to that of the plasma and tissue-free pool. Furthermore, over this period, the increase in the specific radioactivity of proline in collagen and non-collagen protein was linear with respect to time. These results suggest that the large dose of proline floods the precursor pools for protein synthesis, and that this effect can be maintained for quite long periods of time. Such kinetics greatly simplified the method for obtaining collagen synthesis rates in vivo, which were calculated for lung, heart, skin and skeletal muscle, and shown to be quite rapid, ranging between about 3 and 10%/day. The lung was a particularly metabolically active tissue, with synthesis rates of about 10%/day for collagen and 35%/day for total non-collagen proteins, indicating rapid turnover of both intracellular and extracellular proteins of this tissue.

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