scholarly journals Ablation of Leptin Signaling Disrupts the Establishment, Development, and Maintenance of Endometriosis-Like Lesions in a Murine Model

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 506-514 ◽  
Author(s):  
Aaron K. Styer ◽  
Brian T. Sullivan ◽  
Mark Puder ◽  
Danielle Arsenault ◽  
John C. Petrozza ◽  
...  
Keyword(s):  
Murine Model ◽  
Leptin Receptor ◽  
Vascular Endothelial ◽  
Immunocompetent Mouse ◽  
Leptin Signaling ◽  
Peptide Receptor ◽  
Endothelial Growth Factor ◽  
Reproductive Processes ◽  
Insight Into

Leptin, a 16-kDa cytokine, has been implicated in several reproductive processes and disorders. Notably, elevated leptin levels in the peritoneal fluid of women with mild endometriosis has been demonstrated, suggesting a role for this cytokine in the early stages of disease establishment. To gain insight into the functional significance of leptin during the initial requisite proliferative and neovascularization events involved in endometriosis, we investigated the effect of disruption of in vivo leptin signaling on the establishment and/or maintenance of an endometriosis-like lesion in a syngeneic immunocompetent mouse model of endometriosis. Findings of this study show that the disruption of leptin signaling by ip injection of the pegylated leptin peptide receptor antagonist (LPrA) impairs the establishment of endometriosis-like lesions (derived from uteri of C57BL/6 female siblings) and results in a reduction of viable organized glandular epithelium, vascular endothelial growth factor-A expression, and mitotic activity. LPrA treatment resulted in a significant reduction of microvascular density in endometriosis-like lesions after continuous and acute courses. Endometriosis-like lesions (derived from tissue with functional leptin receptor) of Leprdb hosts (nonfunctional leptin receptor) were phenotypically similar to those of LPrA-treated mice. Our results confirm that leptin signaling is a necessary component in lesion proliferation, early vascular recruitment, and maintenance of neoangiogenesis in a murine model of endometriosis.

scholarly journals Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model

2021 ◽  
Vol 22 (2) ◽  
pp. 931
Author(s):  
Jihyun Lee ◽  
Yujin Jung ◽  
Seo won Jeong ◽  
Ga Hee Jeong ◽  
Gue Tae Moon ◽  
...  
Keyword(s):  
Mouse Model ◽  
Signaling Pathway ◽  
Normal Skin ◽  
Skin Lesions ◽  
Hippo Signaling ◽  
Vascular Endothelial ◽  
Expression Levels ◽  
Hippo Signaling Pathway ◽  
Endothelial Growth Factor

The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis. This study investigated the role of the Hippo signaling pathway in the pathogenesis of rosacea. We performed immunohistochemical analyses to compare the expression levels of YAP and TAZ between rosacea skin and normal skin in humans. Furthermore, we used a rosacea-like BALB/c mouse model induced by LL-37 injections to determine the roles of YAP and TAZ in rosacea in vivo. We found that the expression levels of YAP and TAZ were upregulated in patients with rosacea. In the rosacea-like mouse model, we observed that the clinical features of rosacea, including telangiectasia and erythema, improved after the injection of a YAP/TAZ inhibitor. Additionally, treatment with a YAP/TAZ inhibitor reduced the expression levels of YAP and TAZ and diminished vascular endothelial growth factor (VEGF) immunoreactivity in the rosacea-like mouse model. Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea.

scholarly journals Organic Nanocarriers for Bevacizumab Delivery: An Overview of Development, Characterization and Applications

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4127
Author(s):  
Aline de Cristo Soares Alves ◽  
Franciele Aline Bruinsmann ◽  
Silvia Stanisçuaski Guterres ◽  
Adriana Raffin Pohlmann
Keyword(s):  
Monoclonal Antibody ◽  
Physicochemical Characterization ◽  
Vascular Endothelial ◽  
Organic Nanoparticles ◽  
Humanized Monoclonal Antibody ◽  
Angiogenesis Process ◽  
Endothelial Growth Factor ◽  
Drug Pharmacokinetics

Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process. Pathologic angiogenesis is observed in several diseases including ophthalmic disorders and cancer. The multiple administrations of BCZ can cause adverse effects. In this way, the development of controlled release systems for BCZ delivery can promote the modification of drug pharmacokinetics and, consequently, decrease the dose, toxicity, and cost due to improved efficacy. This review highlights BCZ formulated in organic nanoparticles providing an overview of the physicochemical characterization and in vitro and in vivo biological evaluations. Moreover, the main advantages and limitations of the different approaches are discussed. Despite difficulties in working with antibodies, those nanocarriers provided advantages in BCZ protection against degradation guaranteeing bioactivity maintenance.

Effect of co-treatment with doxorubicin and verapamil loaded into chitosan nanoparticles on diethylnitrosamine-induced hepatocellular carcinoma in mice

2020 ◽  
Vol 39 (11) ◽  
pp. 1528-1544 ◽  
Author(s):  
HE Abo Mansour ◽  
MM El-Batsh ◽  
NS Badawy ◽  
ET Mehanna ◽  
NM Mesbah ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Anticancer Activity ◽  
Hepg2 Cells ◽  
Chitosan Nanoparticles ◽  
B Cell Lymphoma ◽  
Favorable Effect ◽  
Vascular Endothelial ◽  
Factor Α ◽  
Endothelial Growth Factor

This study aimed to investigate the potential role of co-treatment with doxorubicin (DOX) and verapamil (VRP) nanoparticles in experimentally induced hepatocellular carcinoma in mice and to investigate the possible mechanisms behind the potential favorable effect of the co-treatment. DOX and VRP were loaded into chitosan nanoparticles (CHNPs), and cytotoxicity of loaded and unloaded drugs against HepG2 cells was evaluated. Male albino mice were divided into eight groups ( n = 15): (1) normal control, (2) diethylnitrosamine, (3) CHNPs, (4) free DOX, (5) CHNPs DOX, (6) free VRP, (7) CHNPs VRP, and (8) CHNPs DOX + CHNPs VRP. Either VRP or DOX loaded into CHNPs showed stronger growth inhibition of HepG2 cells than their free forms. DOX or VRP nanoparticles displayed pronounced anticancer activity in vivo through the decline of vascular endothelial growth factor and B cell lymphoma-2 contents in liver tissues, upregulation of antioxidant enzymes, and downregulation of multidrug resistance 1. Moreover, reduced cardiotoxicity was evident from decreased level of tumor necrosis factor-α and malondialdehyde in heart tissues coupled with decreased serum activity of creatine kinase-myocardial band and lactate dehydrogenase. Co-treatment with CHNPs DOX and CHNPs VRP showed superior results versus other treatments. Liver sections from the co-treatment group revealed the absence of necrosis, enhanced apoptosis, and nearly normal hepatic lobule architecture. Co-treatment with CHNPs DOX and CHNPs VRP revealed enhanced anticancer activity and decreased cardiotoxicity versus the corresponding free forms.

scholarly journals Role of vascular endothelial growth factor in inducing production of angiopoetin-1 – in vivo study in Fisher rats

2017 ◽  
Vol 68 (4) ◽  
pp. 326-329
Author(s):  
Piotr Barć ◽  
Tomasz Płonek ◽  
Dagmara Baczyńska ◽  
Artur Pupka ◽  
Wojciech Witkiewicz ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
In Vivo Study ◽  
Vascular Endothelial ◽  
Angiopoetin 1 ◽  
Endothelial Growth Factor
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