Expression of Angiotensin II Receptor-1 in Human Articular Chondrocytes

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.

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

BioMed Research International ◽

10.1155/2015/273784 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 2

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.

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Expression of endoglin, a TGFβ co-receptor, not ALK5 correlates with the ability of passaged human articular chondrocytes to form cartilage tissue in vitro

Osteoarthritis and Cartilage ◽

10.1016/j.joca.2019.02.057 ◽

2019 ◽

Vol 27 ◽

pp. S40

Author(s):

V.J. Bianchi ◽

M. Parsons ◽

D. Backstein ◽

R. Kandel

Keyword(s):

Articular Chondrocytes ◽

Human Articular Chondrocytes ◽

Cartilage Tissue

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[Leu]enkephalin stimulates carbohydrate metabolism in isolated hepatocytes and kidney tubule fragments by interaction with angiotensin II receptors

Biochemical Journal ◽

10.1042/bj2570705 ◽

1989 ◽

Vol 257 (3) ◽

pp. 705-710 ◽

Cited By ~ 2

Author(s):

S K Hothi ◽

D P Randall ◽

M A Titheradge

Keyword(s):

Angiotensin Ii ◽

Carbohydrate Metabolism ◽

Plasma Membranes ◽

Isolated Hepatocytes ◽

Opioid Peptide ◽

Cross Reactivity ◽

Angiotensin Ii Receptors ◽

Kidney Tubule ◽

Angiotensin Ii Receptor

The possibility that the effects of [Leu]enkephalin in vitro on hepatic carbohydrate metabolism are mediated by interaction with angiotensin II receptors has been examined. Preincubation of hepatocytes with either the angiotensin II receptor antagonist [Sar1,Ile8]angiotensin II or 10 mM-dithiothreitol abolished the ability of both angiotensin II and [Leu]enkephalin to increase phosphorylase a in hepatocytes prepared from fed rats. Dithiothreitol had no effect on the stimulation of phosphorylase in the presence of glucagon or phenylephrine, although it also inhibited the response to vasopressin. [Leu]enkephalin displaced specifically bound 125I-labelled angiotensin II from hepatic plasma membranes over a concentration range of 10(-7)-10(-5) M. This correlated with the dose-response required to stimulate phosphorylase activity in intact hepatocytes and suggests that the effects of the opioid peptides on carbohydrate metabolism in liver are the result of cross-reactivity of the peptides with angiotensin II receptors. Addition of 10(-5) M-[Leu]enkephalin to isolated kidney tubule fragments stimulated gluconeogenesis from 5 mM-pyruvate, the magnitude of stimulation being comparable to that by either angiotensin II or adrenaline. This effect of the opioid peptide was also abolished by pretreatment of the tubules with [Sar1,Ile8]angiotensin II, suggesting that the ability of [Leu]enkephalin to interact with angiotensin II receptors is not restricted to the liver, but may occur in other tissues where both receptors occur together.

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Faculty Opinions recommendation of Transcriptional response of human articular chondrocytes treated with fibronectin fragments: an in vitro model of the osteoarthritis phenotype.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.739123584.793581017 ◽

2020 ◽

Author(s):

Peter Torzilli

Keyword(s):

In Vitro Model ◽

Articular Chondrocytes ◽

Transcriptional Response ◽

Human Articular Chondrocytes ◽

Fibronectin Fragments ◽

Vitro Model

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Selective type 1 angiotensin II receptor blockade attenuates oxidative stress and regulates angiotensin II receptors in the canine failing heart

Molecular and Cellular Biochemistry ◽

10.1007/s11010-008-9835-0 ◽

2008 ◽

Vol 317 (1-2) ◽

pp. 97-104 ◽

Cited By ~ 10

Author(s):

Gordon Moe ◽

Andrea Konig ◽

Peter Liu ◽

Bodh I. Jugdutt

Keyword(s):

Oxidative Stress ◽

Angiotensin Ii ◽

Angiotensin Ii Receptors ◽

Receptor Blockade ◽

Angiotensin Ii Receptor ◽

Failing Heart ◽

Angiotensin Ii Receptor Blockade

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In vitro and in vivo effects of UP 269-6, a new potent orally active nonpeptide angiotensin II receptor antagonist, on vascular smooth muscle cell proliferation

British Journal of Pharmacology ◽

10.1038/sj.bjp.0700897 ◽

1997 ◽

Vol 120 (3) ◽

pp. 488-494 ◽

Cited By ~ 12

Author(s):

A. Virone-Oddos ◽

V. Desangle ◽

D. Provost ◽

M. Cazes ◽

F. Caussade ◽

...

Keyword(s):

Cell Proliferation ◽

Smooth Muscle ◽

Angiotensin Ii ◽

Smooth Muscle Cell ◽

Angiotensin Ii Receptor ◽

Angiotensin Ii Receptor Antagonist ◽

In Vivo Effects ◽

Orally Active

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Low Intensity Shockwave Treatment Modulates Macrophage Functions Beneficial to Healing Chronic Wounds

International Journal of Molecular Sciences ◽

10.3390/ijms22157844 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7844

Author(s):

Jason S. Holsapple ◽

Ben Cooper ◽

Susan H. Berry ◽

Aleksandra Staniszewska ◽

Bruce M. Dickson ◽

...

Keyword(s):

Macrophage Activation ◽

Molecular Mechanisms ◽

Chronic Wounds ◽

Immunohistochemical Analysis ◽

Therapeutic Effects ◽

Gene Expressions ◽

Extracorporeal Shock Wave

Extracorporeal Shock Wave Therapy (ESWT) is used clinically in various disorders including chronic wounds for its pro-angiogenic, proliferative, and anti-inflammatory effects. However, the underlying cellular and molecular mechanisms driving therapeutic effects are not well characterized. Macrophages play a key role in all aspects of healing and their dysfunction results in failure to resolve chronic wounds. We investigated the role of ESWT on macrophage activity in chronic wound punch biopsies from patients with non-healing venous ulcers prior to, and two weeks post-ESWT, and in macrophage cultures treated with clinical shockwave intensities (150–500 impulses, 5 Hz, 0.1 mJ/mm2). Using wound area measurements and histological/immunohistochemical analysis of wound biopsies, we show ESWT enhanced healing of chronic ulcers associated with improved wound angiogenesis (CD31 staining), significantly decreased CD68-positive macrophages per biopsy area and generally increased macrophage activation. Shockwave treatment of macrophages in culture significantly boosted uptake of apoptotic cells, healing-associated cytokine and growth factor gene expressions and modulated macrophage morphology suggestive of macrophage activation, all of which contribute to wound resolution. Macrophage ERK activity was enhanced, suggesting one mechanotransduction pathway driving events. Collectively, these in vitro and in vivo findings reveal shockwaves as important regulators of macrophage functions linked with wound healing. This immunomodulation represents an underappreciated role of clinically applied shockwaves, which could be exploited for other macrophage-mediated disorders.

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