scholarly journals Prothymosin α activates type I collagen to develop a fibrotic placenta in gestational diabetes

2020 ◽  
Vol 134 (18) ◽  
pp. 2435-2445
Author(s):  
Hung-Tsung Wu ◽  
Lin Kang ◽  
Yu-Chu Su ◽  
Horng-Yih Ou ◽  
Fu-Yu Chan ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Type I Collagen ◽  
Fasting Blood Glucose ◽  
Nuclear Factor Κb ◽  
Type I ◽  
Health Issues ◽  
Related Protein ◽  
Prothymosin Α ◽  
Protein Expressions ◽  
Plasma Insulin Levels

Abstract High-risk pregnancies, such as pregnancies with gestational diabetes mellitus (GDM), are becoming more common and as such, have become important public health issues worldwide. GDM increases the risks of macrosomia, premature infants, and preeclampsia. Although placental dysfunction, including fibrosis is associated with the development of GDM, factors that link these observations remain unknown. Prothymosin α (ProTα) is expressed in the placenta and is involved in cell proliferation and immunomodulation. It also plays an important role in insulin resistance and fibrosis. However, the role of ProTα in GDM is still unclear. In the present study, we found that fibrosis-related protein expressions, such as type I collagen (Col-1) were significantly increased in the placentae of ProTα transgenic mice. With elevated fibrosis-related protein expressions, placental weights significantly increased in GDM group. In addition, placental and circulating ProTα levels were significantly higher in patients with GDM (n=39), compared with the healthy group (n=102), and were positively correlated with Col-1 expression. Mice with streptozotocin (STZ)-induced GDM had increased ProTα, fasting blood glucose, Col-1, and placental weight, whereas plasma insulin levels were decreased. ProTα overexpression enhanced nuclear factor κB (NFκB) activation to increase fibrosis-related protein expressions in 3A-Sub-E trophoblasts, while treatment with an NFκB inhibitor reversed the effect of ProTα on fibrosis-related protein expressions. We further investigated whether ProTα is regulated by hyperglycemia-induced reactive oxygen species (ROS). In conclusion, ProTα increases the amount of placental connective tissue and thus contributes to the pathogenesis of placental fibrosis in GDM. Therefore, ProTα may be a novel therapeutic target for GDM.

Gene and Protein Expressions of Type I Collagen are Regulated Tissue-Specifically in Rat Hyaline Cartilages in vivo

2001 ◽  
Vol 39 (3) ◽  
pp. 149-154 ◽  
Author(s):  
Yasuyuki Sasano ◽  
Ichiro Takahashi ◽  
Jing-Xu Zhu ◽  
Haruo Ohtani ◽  
Itaru Mizoguchi ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Type I ◽  
Protein Expressions

scholarly journals Fermented Oyster Extract Prevents Ovariectomy-Induced Bone Loss and Suppresses Osteoclastogenesis

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1392 ◽  
Author(s):  
Hye Jung Ihn ◽  
Ju Ang Kim ◽  
Soomin Lim ◽  
Sang-Hyeon Nam ◽  
So Hyeon Hwang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Type I Collagen ◽  
Therapeutic Option ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Osteoclast Formation ◽  
Type I ◽  
Bioactive Substances

There is growing interest in bioactive substances from marine organisms for their potential use against diverse human diseases. Osteoporosis is a skeletal disorder associated with bone loss primarily occurring through enhanced osteoclast differentiation and resorption. Recently, we reported the anti-osteoclastogenic activity of fermented Pacific oyster (Crassostrea gigas) extract (FO) in vitro. The present study focused on investigating the anti-osteoporotic efficacy of FO in bone loss prevention in an experimental animal model of osteoporosis and elucidating the mechanism underlying its effects. Oral administration of FO significantly decreased ovariectomy-induced osteoclast formation and prevented bone loss, with reduced serum levels of bone turnover biomarkers including osteocalcin and C-terminal telopeptide fragment of type I collagen C-terminus (CTX). FO significantly suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced differentiation of bone marrow-derived macrophages (BMMs) into osteoclasts and attenuated the induction of osteoclast-specific genes required for osteoclastogenesis and bone resorption. Furthermore, FO inhibited RANKL-mediated IκBα and p65 phosphorylation in BMMs. Taken together, these results demonstrate that FO effectively suppresses osteoclastogenesis in vivo and in vitro, and that FO can be considered as a potential therapeutic option for the treatment of osteoporosis and osteoclast-mediated skeletal diseases.

scholarly journals Bovine prolactin-related protein-I is anchored to the extracellular matrix through interactions with type IV collagen

2007 ◽  
Vol 196 (2) ◽  
pp. 225-234 ◽  
Author(s):  
Toru Takahashi ◽  
Osamu Yamada ◽  
Michael J Soares ◽  
Kazuyoshi Hashizume
Keyword(s):  
Extracellular Matrix ◽  
Type Iv Collagen ◽  
Type I Collagen ◽  
Weak Interactions ◽  
Placental Lactogen ◽  
Type I ◽  
Related Protein ◽  
Bovine Placenta ◽  
Type Iv ◽  
Triple Helical Domain

The bovine placenta produces an array of proteins structurally similar to pituitary prolactin (PRL). At least ten genes of the bovine placental PRL family, including bovine placental lactogen (bPL) and ten bovine PRL-related protein-I to -X (bPRP-I to -X), encode hormones/cytokines predicted to be involved in the establishment and maintenance of pregnancy. Targets and biological roles for most members of the bovine PRL family have yet to be specified. This study focused on three members of bovine PRL family, bPL, bPRP-I, and bPRP-VI. An alkaline phosphatase (AP) tagging strategy was used to monitor interactions of the ligands with their targets. AP-bPRP-I and AP-bPRP-VI specifically bound to tissue sections of the bovine placentome. AP-bPRP-I and AP-bPRP-VI binding within the placentome mimicked the distribution of the extracellular matrix (ECM). Consequently, AP fusion protein binding to individual ECM components (heparin, laminin, fibronectin, type I collagen, and type IV collagen) was evaluated. AP-bPRP-I specifically bound to type IV collagen, but not to the other ECM components. AP-bPRP-VI exhibited weak interactions with ECM components, while AP-bPL and AP did not show significant binding to any of the ECM components. Binding of AP-bPRP-I to type IV collagen was concentration-dependent, influenced by salt concentrations, and specific to the N-terminal cross-linking domain (7S) of type IV collagen but not its triple-helical domain. The interaction of bPRP-I with type IV collagen suggests that bPRP-I accumulates in the ECM where it likely acts on cells traversing the bovine placentome.

scholarly journals Acute changes in serum osteoprotegerin and receptor activator for nuclear factor-κB ligand levels in women with established osteoporosis treated with teriparatide

2008 ◽  
Vol 158 (3) ◽  
pp. 411-415 ◽  
Author(s):  
Athanasios D Anastasilakis ◽  
Dimirtios G Goulis ◽  
Stergios A Polyzos ◽  
Spiridon Gerou ◽  
Vasiliki Pavlidou ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Serum Levels ◽  
Nuclear Factor Κb ◽  
Acute Effect ◽  
Type I ◽  
Nuclear Factor ◽  
Mineral Density ◽  
Serum Samples ◽  
Established Osteoporosis ◽  
Receptor Activator

ObjectiveThe mechanisms regulating the anabolic response of the skeleton to intermittent exogenous parathyroid hormone (PTH) administration are not fully elucidated. The aim of this prospective study was to evaluate the acute effect (up to 1 month) of teriparatide (TPTD; human recombinant PTH 1–34) on serum levels of osteoprotegerin (OPG) and receptor activator for nuclear factor-κB ligand (RANKL) in women with established osteoporosis.DesignTwenty-three postmenopausal Caucasian women with established osteoporosis (mean age 66.7±1.6 years) received daily injections of 20 μg TPTD for 12 months.MethodsSerum samples for total calcium (Ca), phosphate, alkaline phosphatase, N-terminal propeptide of type I collagen, intact PTH (iPTH), OPG, and RANKL were obtained at baseline, 1 h, 1 day, and 1 month after initiation of therapy. Lumbar spine bone mineral density (BMD) was measured before and 12 months after TPTD treatment.ResultsSerum total Ca increased and iPTH gradually decreased with TPTD treatment. Serum OPG levels remained unchanged, while RANKL increased gradually during the study (P<0.001). There was no correlation between OPG or RANKL and BMD changes or iPTH levels.ConclusionsTPTD therapy in women with postmenopausal osteoporosis results in acute increase in serum RANKL levels but does not affect serum OPG. These changes may reflect an increase in the number of active osteoblasts with therapy and might be responsible for the acceleration of bone turnover rate that characterizes TPTD.

A Hypothesis for the Anti-Inflammatory and Mechanotransduction Molecular Mechanisms Underlying Acupuncture Tendon Healing

2014 ◽  
Vol 32 (2) ◽  
pp. 178-182 ◽  
Author(s):  
Marcos dos Santos de Almeida ◽  
Flávia Da Ré Guerra ◽  
Letícia Prado de Oliveira ◽  
Cristiano Pedrozo Vieira ◽  
Edson Rosa Pimentel
Keyword(s):  
Collagen Synthesis ◽  
Molecular Mechanisms ◽  
Type I Collagen ◽  
Tendon Healing ◽  
Nuclear Factor Κb ◽  
Therapeutic Effects ◽  
Molecular Pathways ◽  
Type I ◽  
Activity Levels ◽  
Anti Inflammatory

A previous study demonstrated that acupuncture increases the synthesis and reorganisation of collagen molecules in rat tendons after injury. Clinical studies have shown that acupuncture improves pain and functional activity in patients with tendinopathy. However, the molecular mechanisms underlying these effects are unknown. Recent studies have shown that acupuncture can modulate both anti-inflammatory (AI) and mechanotransduction (MT) molecular pathways. Moreover, the modulation of these pathways can increase type I collagen synthesis, which is the main factor that influences tendon biomechanical properties. Our hypothesis is that acupuncture increases synthesis and subsequent reorganisation of type I collagen during tendon healing by concomitant modulation of the Toll-like receptor-nuclear factor-κB AI pathway, the mitogen-activated protein kinases pathway and the Rho/Rac-F-actin MT pathway. Increased collagen synthesis and reorganisation requires that at least one acupoint is anatomically connected with the site of the injury because of the local tenoblast MT mechanism. Confirmation of this hypothesis will increase the knowledge of acupuncture modulation of the previously mentioned molecular pathways, and such confirmation may also help to establish the relationships between the different types of acupuncture needle stimulation and the influence of acupuncture stimuli on pathway activity levels. In addition, the downstream therapeutic effects of acupuncture therapy may be established. This hypothesis can be verified in a rat tendon healing model, and subsequent clinical protocols for tendon healing can be developed and evaluated as standalone therapies or as a component of a combination therapy.

scholarly journals Bone Metabolism and RANKL/OPG Ratio in Rheumatoid Arthritis Women Treated with TNF-α Inhibitors

2021 ◽  
Vol 10 (13) ◽  
pp. 2905
Author(s):  
Agnieszka Jura-Półtorak ◽  
Anna Szeremeta ◽  
Krystyna Olczyk ◽  
Aleksandra Zoń-Giebel ◽  
Katarzyna Komosińska-Vassev
Keyword(s):  
Bone Metabolism ◽  
Type I Collagen ◽  
Serum Levels ◽  
Nuclear Factor Κb ◽  
Type I ◽  
Mineral Density ◽  
Type I Procollagen ◽  
Tnf Α ◽  
C And N ◽  
Turnover Markers

The aim of this study was to evaluate the effect of anti-tumor necrosis factor α (anti-TNF-α) therapy in combination with methotrexate on bone remodeling and osteoclastogenesis in female patients with RA. Serum levels of bone turnover markers (i.e., C- and N-terminal propeptides of type I procollagen (PICP and PINP), C- and N-terminal cross-linking telopeptides of type I collagen (CTX-I and NTX-I), and soluble receptor activator of nuclear factor κB ligand (sRANKL) and osteoprotegerin (OPG)) were determined by immunoassay at baseline and 15 months after initiation of treatment. Bone mineral density was measured by dual-energy x-ray absorptiometry. We found a significant decrease in serum PINP levels, a biomarker of bone formation, and higher levels of CTX-I and sRANKL indicative of increased bone resorption in RA patients prior to TNFαI treatment compared to the controls. Anti-TNF-α therapy was effective in improving bone metabolism in RA patients as reflected in a decrease in CTX-I (at least partially due to the RANKL/OPG reduction) and a concomitant increase in PINP levels. The bone metabolism changes were independent of the type of TNFαI used. PINP and CTX-I were found to be useful markers of bone metabolism, which may prove the effectiveness of TNF-α therapy earlier than the bone density assessment.

Collagen fibrillogenesis in vitro: interaction of types I and V collagen

1986 ◽  
Vol 44 ◽  
pp. 210-211
Author(s):  
Arthur J. Wasserman ◽  
Kathy C. Kloos ◽  
David E. Birk
Keyword(s):  
Type I Collagen ◽  
Corneal Stroma ◽  
Minor Component ◽  
Homogeneous Distribution ◽  
Type I ◽  
Type V Collagen ◽  
Fibril Morphology ◽  
Type V ◽  
In Vitro Interaction

Type I collagen is the predominant collagen in the cornea with type V collagen being a quantitatively minor component. However, the content of type V collagen (10-20%) in the cornea is high when compared to other tissues containing predominantly type I collagen. The corneal stroma has a homogeneous distribution of these two collagens, however, immunochemical localization of type V collagen requires the disruption of type I collagen structure. This indicates that these collagens may be arranged as heterpolymeric fibrils. This arrangement may be responsible for the control of fibril diameter necessary for corneal transparency. The purpose of this work is to study the in vitro assembly of collagen type V and to determine whether the interactions of these collagens influence fibril morphology.

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