scholarly journals Candesartan Mediated Amelioration of Cisplatin-Induced Testicular Damage Is Associated with Alterations in Expression Patterns of Nephrin and Podocin

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Noritoshi Enatsu ◽  
Hideaki Miyake ◽  
Koji Chiba ◽  
Masato Fujisawa
Keyword(s):  
Angiotensin Ii ◽  
Marked Decrease ◽  
Expression Patterns ◽  
Basal Membrane ◽  
Seminiferous Tubules ◽  
Angiotensin Ii Receptor Blocker ◽  
Testicular Damage ◽  
Angiotensin Ii Receptor

Nephrin and podocin are known to be closely related to the pharmacological effects of angiotensin-II receptor blocker (ARB). The objectives of this study were to investigate the role of nephrin and podocin using cisplatin-induced testicular damage and to evaluate the effect of ARB. At first, we evaluated the effects of cisplatin either alone or in combination with ARB candesartan on changes in expression patterns of nephrin and podocin in the rat testes. We then conductedin vitrostudies to investigate the effects of angiotensin using cultured Sertoli cells, line TM4. As a result, the expression of nephrin and podocin was shown to localize around the basal membrane of seminiferous tubules. Treatment with cisplatin resulted in a marked decrease in the expression of nephrin and podocin and induced a shift of both proteins from linear to granular expression patterns, accompanying the increased apoptotic index in the testes; these changes were partially restored by the additional administration of candesartan.In vitrostudies with TM4 revealed the angiotensin-II mediated expression changes of nephrin and podocin. These findings suggest that candesartan can prevent cisplatin-induced testicular damage by regulating expression patterns of the nephrin-podocin complex in the testes.

scholarly journals The C-X-C signalling system in the rodent vs primate testis: impact on germ cell niche interaction

Reproduction ◽  
2018 ◽  
Vol 155 (5) ◽  
pp. R211-R219 ◽  
Author(s):  
Laura Heckmann ◽  
Tim Pock ◽  
Ina Tröndle ◽  
Nina Neuhaus
Keyword(s):  
Germ Cell ◽  
Transmembrane Domain ◽  
Basal Membrane ◽  
Seminiferous Tubules ◽  
Testicular Development ◽  
Signalling System ◽  
Evolutionarily Conserved

In zebrafish, action of the chemokine Cxcl12 is mediated through its G-protein-coupled seven-transmembrane domain receptor Cxcr4 and the atypical receptor Cxcr7. Employing this animal model, it was revealed that this Cxcl12 signalling system plays a crucial role for directed migration of primordial germ cells (PGC) during early testicular development. Importantly, subsequent studies indicated that this regulatory mechanism is evolutionarily conserved also in mice. What is more, the functional role of the CXCL12 system does not seem to be limited to early phases of testicular development. Data from mouse studies rather demonstrate that CXCL12 and its receptors are also involved in the homing process of gonocytes into their niches at the basal membrane of the seminiferous tubules. Intriguingly, even the spermatogonial stem cells (SSCs) present in the adult mouse testis appear to maintain the ability to migrate towards a CXCL12 gradient as demonstrated by functional in vitro migration assays and in vivo germ cell transplantation assays. These findings not only indicate a role of the CXCL12 system throughout male germ cell development in mice but also suggest that this system may be evolutionarily conserved. In this review, we take into account the available literature focusing on the localization patterns of the CXCL12 system not only in rodents but also in primates, including the human. Based on these data, we discuss whether the CXCL12 system is also conserved between rodents and primates and discuss the known and potential functional consequences.

scholarly journals Potential role of ACE2 in coronavirus disease 2019 (COVID-19) prevention and management

2020 ◽  
Vol 8 (1) ◽  
pp. 9-19 ◽  
Author(s):  
Mengyuan Liu ◽  
Ting Wang ◽  
Yun Zhou ◽  
Yutong Zhao ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Potential Role ◽  
Human Monoclonal Antibody ◽  
Harmful Effect ◽  
Spike Protein ◽  
Angiotensin Ii Receptor Blocker ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Novel Coronavirus

AbstractCOVID-19 is the current public health threat all over the world. Unfortunately, there is no specific prevention and treatment strategy for this disease. We aim to explore the potential role of angiotensin-converting enzyme 2 (ACE2) in this regard through this literature review. As a crucial enzyme of renin-angiotensin-aldosterone system (RAAS), ACE2 not only mediates the virus entry but also affects the pathophysiological process of virus-induced acute lung injury (ALI), as well as other organs’ damage. As interaction of COVID-19 virus spike and ACE2 is essential for virus infection, COVID-19-specific vaccine based on spike protein, small molecule compound interrupting their interaction, human monoclonal antibody based on receptor-binding domain, and recombinant human ACE2 protein (rhuACE2) have aroused the interests of researchers. Meanwhile, ACE2 could catalyze angiotensin II (Ang II) to form angiotensin 1-7 (Ang 1-7), thus alleviates the harmful effect of Ang II and amplifies the protection effect of Ang1-7. ACE inhibitor and angiotensin II receptor blocker (ARB) have been shown to increase the level of expression of ACE2 and could be potential strategies in protecting lungs, heart, and kidneys. ACE2 plays a very important role in the pathogenesis and pathophysiology of COVID-19 infection. Strategies targeting ACE2 and its ligand, COVID-19 virus spike protein, may provide novel method in the prevention and management of novel coronavirus pneumonia.

scholarly journals Expression of Angiotensin II Receptor-1 in Human Articular Chondrocytes

Arthritis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Yuki Kawakami ◽  
Kosuke Matsuo ◽  
Minako Murata ◽  
Kazuo Yudoh ◽  
Hiroshi Nakamura ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Articular Chondrocytes ◽  
Cartilage Damage ◽  
Immunohistochemical Analysis ◽  
Human Articular Chondrocytes ◽  
Cartilage Tissue ◽  
Angiotensin Ii Receptors ◽  
Angiotensin Ii Receptor

Background. Besides its involvement in the cardiovascular system, the renin-angiotensin-aldosterone (RAS) system has also been suggested to play an important role in inflammation. To explore the role of this system in cartilage damage in arthritis, we investigated the expression of angiotensin II receptors in chondrocytes. Methods. Articular cartilage was obtained from patients with osteoarthritis, rheumatoid arthritis, and traumatic fractures who were undergoing arthroplasty. Chondrocytes were isolated and cultured in vitro with or without interleukin (IL-1). The expression of angiotensin II receptor types 1 (AT1R) and 2 (AT2R) mRNA by the chondrocytes was analyzed using reverse transcription-polymerase chain reaction (RT-PCR). AT1R expression in cartilage tissue was analyzed using immunohistochemistry. The effect of IL-1 on AT1R/AT2R expression in the chondrocytes was analyzed by quantitative PCR and flow cytometry. Results. Chondrocytes from all patient types expressed AT1R/AT2R mRNA, though considerable variation was found between samples. Immunohistochemical analysis confirmed AT1R expression at the protein level. Stimulation with IL-1 enhanced the expression of AT1R/AT2R mRNA in OA and RA chondrocytes. Conclusions. Human articular chondrocytes, at least partially, express angiotensin II receptors, and IL-1 stimulation induced AT1R/AT2R mRNA expression significantly.

scholarly journals The Angiotensin II Receptor Blocker Losartan Sensitizes Human Liver Cancer Cells to Lenvatinib-Mediated Cytostatic and Angiostatic Effects

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 575
Author(s):  
Hirotetsu Takagi ◽  
Kosuke Kaji ◽  
Norihisa Nishimura ◽  
Koji Ishida ◽  
Hiroyuki Ogawa ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cell Growth ◽  
Low Dose ◽  
Receptor Blocker ◽  
Tumor Xenograft ◽  
Angiotensin Ii Receptor Blocker ◽  
G1 Arrest ◽  
Advanced Hepatocellular Carcinoma ◽  
Angiotensin Ii Receptor

Molecular targeted therapy with lenvatinib is commonly offered to advanced hepatocellular carcinoma (HCC) patients, although it is often interrupted by adverse effects which require a reduction in the initial dose. Thus, an alternative lenvatinib-based therapy to compensate for dose reduction is anticipated. This study aimed to assess the effect of combination of low-dose of lenvatinib and the angiotensin-II (AT-II) receptor blocker losartan on human HCC cell growth. In vitro studies found that losartan suppressed the proliferation by inducing G1 arrest and caused apoptosis as indicated by the cleavage of caspase-3 in AT-II-stimulated HCC cell lines (Huh-7, HLE, and JHH-6). Losartan attenuated the AT-II-stimulated production of vascular endothelial growth factor-A (VEGF-A) and interleukin-8 and suppressed lenvatinib-mediated autocrine VEGF-A production in HCC cells. Moreover, it directly inhibited VEGF-mediated endothelial cell growth. Notably, the combination of lenvatinib and losartan augmented the cytostatic and angiostatic effects of the former at a low-dose, reaching those achieved with a conventional dose. Correspondingly, a HCC tumor xenograft assay showed that the oral administration of losartan combined with lenvatinib reduced the subcutaneous tumor burden and intratumor vascularization in BALB/c nude mice. These findings support that this regimen could be a viable option for patients intolerant to standard lenvatinib dosage.

scholarly journals Effect of Dietary Fiber on the Level of Free Angiotensin II Receptor Blocker in Vitro

2014 ◽  
Vol 37 (5) ◽  
pp. 779-784 ◽  
Author(s):  
Ayano Iwazaki ◽  
Kazuhiro Takahashi ◽  
Yui Tamezane ◽  
Kenta Tanaka ◽  
Minami Nakagawa ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Dietary Fiber ◽  
Receptor Blocker ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor
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