CT-1 induces angiogenesis by regulating the ADMA/DDAH Pathway

Zheng, Zizhan; Xiao, Fu; Jin, Liang; Guo, Zhi

doi:10.5507/bp.2015.009

Cited by 5 publications

(4 citation statements)

References 12 publications

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“…CT-1 is a member belonging to IL-6 superfamily (35). By interacting with the heterodimer comp osed of glycoprotein 130 and leukemia inhibitory factor receptor-β, this cytokine exerts a series of cellular effects (36).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of cardiotrophin-1 overexpression is involved in the anti-fibrotic effect of Astrogaloside IV

Jia

Leng

Wang

et al. 2017

Molecular Medicine Reports

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Astragaloside IV (AsIV), one of the major active ingredients in Astragalus membranaceus, has demonstrated remarkable antifibrotic effects via its antioxidative activity. Cardiac fibrosis is an important pathological mechanism during cardiac remodelling associated with heart failure. In the present study, the mechanism underlying the antifibrotic effect of AsIV upon isoprenaline (ISO) stimulation was investigated. AsIV significantly improved cardiac fibrosis in vivo and dose‑dependently inhibited ISO‑induced CF proliferation in vitro. The ISO‑triggered elevation in reactive oxygen species (ROS) levels was remarkably inhibited by AsIV, as well as ROS scavenger N‑acetylcysteine (NAC), and not affected by cardiotrophin‑1 (CT‑1) knockdown. In addition, AsIV effectively reversed ISO‑induced upregulation of CT‑1 expression, which was blunted by pretreatment with NAC. Cardiac fibroblast (CF) proliferation and collagen Ι overexpression induced by ISO stimulation were effectively abrogated by AsIV, NAC, and CT‑1 small interfering RNA transfection. Taken together, these results demonstrated that AsIV was able to effectively inhibit ISO‑induced CF proliferation and collagen production through negative regulation of ROS‑mediated CT‑1 upregulation.

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Section: Discussionmentioning

confidence: 99%

Inhibition of cardiotrophin-1 overexpression is involved in the anti-fibrotic effect of Astrogaloside IV

Jia

Leng

Wang

et al. 2017

Molecular Medicine Reports

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“…CTF1 has been identified as an important regulator of cardiac, renal, hepatic, and nervous system functionality that has also recently been detected in the murine endometrium during the early stages of pregnancy ( Kobayashi et al, 2014 ). At a functional level, this cytokine is known to promote endothelial cell and neuronal survival, proliferation, migration, and differentiation, and it can also promote MSC persistence following injection into a particular tissue site ( Zheng et al, 2015 ; Bortolotti et al, 2017 ). Yang et al (2008) determined that CTF1 treatment was linked to transient increases in microvessel density and VEGF production, suggesting that these two cytokines influence one another to drive angiogenic processes.…”

Section: Discussionmentioning

confidence: 99%

“…For example, Yang et al determined that CTF1 was able to enhance tissue regeneration in the context of liver cirrhosis by promoting cellular proliferation and angiogenesis ( Yang et al, 2008 ), consistent with evidence that CTF1 overexpression using an adenoviral vector can improve liver function and survival associated with small-for-size grafts ( Song et al, 2008 ). Such CTF1 expression has been shown to drive the proliferative, migratory, and angiogenic activity of endothelial cells via the ADMA/DDAH pathway ( Zheng et al, 2015 ). Kobayashi et al (2014) further employed an in vivo functional screening approach that identified CTF1 as an important promoter of successful embryo implantation.…”

Section: Introductionmentioning

confidence: 99%

Exosomes Derived From CTF1-Modified Bone Marrow Stem Cells Promote Endometrial Regeneration and Restore Fertility

Zhu

Tang

Zhu

et al. 2022

Front. Bioeng. Biotechnol.

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Background: Thin endometrial tissue is a leading cause of embryo transfer failure, potentially contributing to sustained infertility and associated adverse outcomes. The application of exosomes derived from autologous or allogeneic bone marrow-derived stem cells (BMSCs) has been used to promote uterine repair following injury, and there is also prior evidence that stem cell transplantation can bolster fertility. Genetic modifications represent a primary approach to enhancing exosomal therapy strategies. The present study thus explored the effects of Cardiotrophin-1 (CTF1)-modified BMSCs-exo on fertility-related outcomes.Methods: An adenoviral vector was used to generate CTF1-overexpressing BMSCs (C-BMSCs), after which exosomes were isolated from control BMSCs (BMSC-exos) and C-BMSCs (C-BMSC-exos). The angiogenic effects of C-BMSC-exo treatment were assessed through analyses of endothelial cell proliferation and tube formation. Model rats exhibiting endometrial thinning were administered C-BMSCs-exo, after which the effects of such treatment were assessed through H&E staining, Masson’s trichrome staining, and immunofluorescence analyses. The mechanistic basis for the proangiogenic effects of CTF1 as a driver of endometrial regeneration was additionally explored.Results: C-BMSC-exo treatment of HUVECs was associated with enhanced neovascularization, as evidenced by improved in vitro proliferation, migration, and tube formation. Importantly, such treatment was also linked to tissue regeneration, neovascularization, and the suppression of localized tissue fibrosis in vivo. Regenerated endometrial tissue exhibited higher embryo receptivity and was associated with higher birth rates in treated rats. The upregulation of the JAK/PI3K/mTOR/STAT3 signaling pathways in C-BMSC-exo-treated rats may underscore the mechanistic basis whereby CTF1 can positively impact endometrial angiogenesis and regeneration.Conclusion: Our data suggest that exosomes produced by CTF1-modified BMSCs can more effectively promote the regeneration of endometrial and myometrial tissues, driving neovascularization in a manner that improves endometrial receptivity in a rat model system, highlighting the therapeutic promise of this approach for patients diagnosed with endometrial thinning.

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“…The direct atherogenic effects of CT-1 on vascular wall cells are shown in Figure 3. CT-1 stimulates the migration and proliferation of human umbilical vein ECs [64], which contributes to atherogenesis as well as angiogenesis. CT-1 stimulates the synthesis of inflammatory cytokines and proatherogenic molecules, such as IL-6, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, and MMP-1, in human ECs [26,[65][66][67].…”

Section: Atheroprone Effects Of Ct-1mentioning

confidence: 99%

Emerging Roles of Cardiotrophin-1 in the Pathogenesis and Biomarker of Atherosclerosis

Watanabe

Konii

Sato

2018

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Cardiotrophin-1 (CT-1), an interleukin-6 family cytokine, is known as an active inducer capable of cardiac hypertrophy and vascular stiffness in hypertensive heart disease. CT-1 is expressed at high levels in the heart, vascular endothelial cells (ECs), and adipocytes. CT-1 stimulates inflammatory and proatherogenic molecule expression in human monocytes and ECs, as well as monocyte-EC adhesion. CT-1 enhances oxidized low-density lipoprotein-induced foam-cell formation in human monocyte-derived macrophages. CT-1 stimulates the migration, proliferation, and colloagen-1 production in human vascular smooth muscle cells. Chronic CT-1 infusion into Apoe −/− mice accelerates the development of aortic atherosclerotic lesions. CT-1 is expressed at high levels in ECs and macrophage foam cells within atheromatous plaques in Apoe −/− mice. A blockade of CT-1 using anti-CT-1 neutralizing antibody results in the prevention of atherogenesis in Apoe −/− mice. Plasma CT-1 concentrations are elevated in patients with hypertensive heart disease, ischemic heart disease, and metabolic syndrome, and are positively associated with the severity of cardiac hypertrophy, heart failure, and atherosclerosis. Increased plasma concentration of CT-1 is a predictor of death and heart failure following acute myocardial infarction. Therefore, CT-1 serves a novel therapeutic target for atherosclerosis and related diseases. Plasma CT-1 may be a reliable biomarker for atherosclerotic cardiovascular diseases.J 2018, 1 95 have provided the first evidence that CT-1 is expressed at high levels in atherosclerotic lesions and shows proatherogenic effects [15]. Other studies have reported that plasma concentrations of CT-1 are increased in patients with coronary artery disease (CAD) [16].The present review introduces the recent accumulating evidence regarding the roles of CT-1 in the pathophysiology of atherosclerosis and the potential biomarker of cardiovascular and metabolic diseases. Structure, Expression, and Function of CT-1CT-1 is a new member of the interleukin (IL)-6 cytokine family that was originally cloned from a mouse embryoid body cDNA library based on its ability to induce hypertrophy in neonatal cardiomyocytes [17]. cDNA clones of human CT-1 were isolated by screening a heart cDNA library with a mouse CT-1 probe [17]. The DNA sequence of these clones encodes a protein of 201 amino acids that is 80% identical with the 203 amino acid residue of mouse CT-1 [18]. CT-1 has a molecular weight of 21.5 kDa. Human and mouse CT-1 lack a conventional, hydrophobic, N-terminal amino acid sequence indicative of a secretion signal [18]. The amino acid sequence of rat CT-1 is 80% and 94% identical to those of human CT-1 and mouse CT-1, respectively [19]. The coding region of CT-1 is contained on 3 exons and is located on human chromosome 16p11.1-16p11.2 [18].CT-1 is expressed in the cardiovascular system as well as the brain, thymus, lungs, kidneys, liver, intestine, testes, prostate, skeletal muscles, and adipose tissue [18][19][20][21][22][23]. In cardiov...

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CT-1 induces angiogenesis by regulating the ADMA/DDAH Pathway

Cited by 5 publications

References 12 publications

Inhibition of cardiotrophin-1 overexpression is involved in the anti-fibrotic effect of Astrogaloside IV

Inhibition of cardiotrophin-1 overexpression is involved in the anti-fibrotic effect of Astrogaloside IV

Exosomes Derived From CTF1-Modified Bone Marrow Stem Cells Promote Endometrial Regeneration and Restore Fertility

Emerging Roles of Cardiotrophin-1 in the Pathogenesis and Biomarker of Atherosclerosis

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