scholarly journals Functional genomic screen identifies novel mediators of collagen uptake

2014 ◽  
Vol 25 (5) ◽  
pp. 583-593 ◽  
Author(s):  
Ting-Hein Lee ◽  
William McKleroy ◽  
Amin Khalifeh-Soltani ◽  
Stephen Sakuma ◽  
Stanislav Lazarev ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Human Monocyte ◽  
Mannose Receptor ◽  
Type I ◽  
Collagen Turnover ◽  
Proteolytic Pathway ◽  
A Genome ◽  
Intracellular Pathways ◽  
Main Component ◽  
Intracellular Pathway

Tissue fibrosis occurs when matrix production outpaces matrix degradation. Degradation of collagen, the main component of fibrotic tissue, is mediated through an extracellular proteolytic pathway and intracellular pathway of cellular uptake and lysosomal digestion. Recent studies demonstrate that disruption of the intracellular pathways can exacerbate fibrosis. These pathways are poorly characterized. Here we identify novel mediators of the intracellular pathway of collagen turnover through a genome-wide RNA interference screen in Drosophila S2 cells. Screening of 7505 Drosophila genes conserved among metazoans identified 22 genes that were required for efficient internalization of type I collagen. These included proteins involved in vesicle transport, the actin cytoskeleton, and signal transduction. We show further that the flotillin genes have a conserved and central role in collagen uptake in Drosophila and human cells. Short hairpin RNA–mediated silencing of flotillins in human monocyte and fibroblasts impaired collagen uptake by promoting lysosomal degradation of the endocytic collagen receptors uPARAP/Endo180 and mannose receptor. These data provide an initial characterization of intracellular pathways of collagen turnover and identify the flotillin genes as critical regulators of this process. A better understanding of these pathways may lead to novel therapies that reduce fibrosis by increasing collagen turnover.

scholarly journals Responses of Markers of Bone and Collagen Turnover to Exercise, Growth Hormone (GH) Administration, and GH Withdrawal in Trained Adult Males1

2000 ◽  
Vol 85 (1) ◽  
pp. 124-133 ◽  
Author(s):  
Jennifer D. Wallace ◽  
Ross C. Cuneo ◽  
Per Arne Lundberg ◽  
Thord Rosén ◽  
Jens Otto Lunde Jørgensen ◽  
...  
Keyword(s):  
Acute Exercise ◽  
Type I Collagen ◽  
Controlled Study ◽  
Bone Resorption Marker ◽  
Type I ◽  
Serum Osteocalcin ◽  
Collagen Turnover ◽  
Gh Treatment ◽  
Type I Procollagen ◽  
Procollagen Iii

To examine the interactions between acute exercise and GH on markers of bone and collagen turnover and to assess the potential for detecting GH abuse in athletes using these markers, we studied 17 aerobically trained males (age, 26.9 ± 1.5 yr). Sequential studies of exercise, GH administration, and GH withdrawal were undertaken. A randomized, controlled study of rest vs. exercise showed that exercise did not change serum osteocalcin; other markers of formation increased transiently (each P < 0.001): bone-specific alkaline phosphatase (+16.1%), carboxyterminal propeptide of type I procollagen (+14.1%), and procollagen III N-terminal extension peptide (+5.0%). The carboxyterminal cross-linked telopeptide of type I collagen, a bone resorption marker, increased 9.7% (P = 0.018) in response to exercise. A randomized, double blind, placebo-controlled, parallel study of recombinant human GH treatment (0.15 IU/kg·day) for 1 week increased serum osteocalcin (net increase preexercise, +10.0%; P = 0.017), carboxyterminal propeptide of type I procollagen (+17.6%; P = 0.002), procollagen III N-terminal extension peptide (+48.4%; P = 0.001), and carboxyterminal cross-linked telopeptide of type I collagen (53.3%; P = 0.009). Disappearance half-times after cessation of recombinant human GH for pre- and postexercise markers ranged from 248–770 h. We conclude 1) endurance exercise transiently activates bone and collagen turnover; 2) brief GH administration results in similar but quantitatively greater augmentation; and 3) these data will assist in designing a GH detection strategy.

scholarly journals Matrix metalloproteinase-degraded type I collagen is associated with APOE/TOMM40 variants and preclinical dementia

2020 ◽  
Vol 6 (5) ◽  
pp. e508
Author(s):  
Man-Hung Eric Tang ◽  
Joseph P.M. Blair ◽  
Cecilie Liv Bager ◽  
Anne-Christine Bay-Jensen ◽  
Kim Henriksen ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Matrix Metalloproteinase ◽  
Gene Cluster ◽  
Type I Collagen ◽  
Early Death ◽  
Collagen Metabolism ◽  
Type I ◽  
Age Related ◽  
Genome Wide ◽  
A Genome

ObjectiveDysregulation of type I collagen metabolism has a great impact on human health. We have previously seen that matrix metalloproteinase–degraded type I collagen (C1M) is associated with early death and age-related pathologies. To dissect the biological impact of type I collagen dysregulation, we have performed a genome-wide screening of the genetic factors related to type I collagen turnover.MethodsPatient registry data and genotypes have been collected for a total of 4,981 Danish postmenopausal women. Genome-wide association with serum levels of C1M was assessed and phenotype-genotype association analysis performed.ResultsTwenty-two genome-wide significant variants associated with C1M were identified in the APOE-C1/TOMM40 gene cluster. The APOE-C1/TOMM40 gene cluster is associated with hyperlipidemia and cognitive disorders, and we further found that C1M levels correlated with tau degradation markers and were decreased in women with preclinical cognitive impairment.ConclusionsOur study provides elements for better understanding the role of the collagen metabolism in the onset of cognitive impairment.

scholarly journals Effect of magnesium ions/Type I collagen promote the biological behavior of osteoblasts and its mechanism

2019 ◽  
Author(s):  
Xiaojing Nie ◽  
Xirao Sun ◽  
Chengyue Wang ◽  
Jingxin Yang
Keyword(s):  
Type I Collagen ◽  
Bone Development ◽  
Critical Role ◽  
Biological Behavior ◽  
Type I ◽  
Alizarin Red ◽  
Downstream Signaling ◽  
Proliferation And Differentiation ◽  
Main Component ◽  
Rhodamine B Isothiocyanate

Abstract Type I collagen (Col I) is a main component of extracellular matrix (ECM). Its safety, biocompatibility, hydrophilicity and pyrogen immunogenicity make it suitable for tissues engineering applications. Mg2+ also control a myriad of cellular processes, including the bone development by enhancing the attachment and differentiation of osteoblasts and accelerating mineralization to enhance bone healing. In our studies, Mg2+ bind collagen to promote the proliferation and differentiation of osteoblasts through the expression of integrins and downstream signaling pathways. In order to clarify the biological behavior effect of 10 mM Mg2+/Col I coating, we performed 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), alkaline phosphatase (ALP), 4′6-diamidino-2-phenylindole (DAPI), Alizarin red staining and Rhodamine B-isothiocyanate (RITC)-labeled phalloidin experiments and found that 10 mM Mg2+ group, Col I-coating group, 10 mM Mg2+/Col I-coating group, respectively, promoted the proliferation and differentiation of osteoblasts, especially 10 mM Mg2+/Col I-coating group. We detected the mRNA expression of osteogenic-related genes (Runx2, ALP and OCN, OPN and BMP-2) and the protein expression of signaling pathway (integrin α2, integrin β1, FAK and ERK1/2), these results indicated that 10 mM Mg2+/Col I coating play an critical role in up-regulating the MC3T3-E1 cells activity. The potential mechanisms of this specific performance may be through activating via integrin α2β1-FAK-ERK1/2 protein-coupled receptor pathway.

Type I collagen turnover is a critical parameter for melanoma progression

2006 ◽  
Vol 16 (Supplement 1) ◽  
pp. S71 ◽  
Author(s):  
L. van Kempen ◽  
J. Rijntjes ◽  
I. Mamor-Cornelissen ◽  
S. Vincent-Naulleau ◽  
M. Gerritsen ◽  
...  
Keyword(s):  
Critical Parameter ◽  
Type I Collagen ◽  
Type I ◽  
Collagen Turnover ◽  
Melanoma Progression

scholarly journals THE ROLE OF MATRIX METALLOPROTEINASE (MMP)-2 TO TYPE I COLLAGEN TURNOVER CONTRIBUTING TO HYPERTROPHIC ARTERIAL REMODELING IN RENOVASCULAR HYPERTENSION

2021 ◽  
Vol 39 (Supplement 1) ◽  
pp. e389
Author(s):  
Viviano Gomes de Neves ◽  
Marcela Maria Blascke de Mello ◽  
Pedro Henrique L Silva ◽  
Laena Pernomian ◽  
Juliana Monteneg Parente ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Renovascular Hypertension ◽  
Type I Collagen ◽  
Type I ◽  
Arterial Remodeling ◽  
Collagen Turnover

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.

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