Human renal mesangial cells are a target for the anti‐inflammatory action of 9‐cis retinoic acid

Manzano, Victoria Moreno; Muñoz, Javier Cuenca; Jimenez, Jenyfer; Puyol, Manuel Rodríguez; Puyol, Diègo Rodrı́guez; Kitamura, Masanori; Lucio-Cazaña, Javier

doi:10.1038/sj.bjp.0703728

Cited by 32 publications

(25 citation statements)

References 56 publications

(66 reference statements)

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“…For example, RXR agonists inhibited apoptosis in human mesangial cells exposed to H 2 O 2 and naive tlymphocytes. [14,15] However, they facilitated apoptosis in tumor cells, such as lung and breast carcinomas, lymphomas, and leukemias. [16][17][18] Thus, there is controversy over pro-or anti-apoptotic effect, which may depend on the type of cells and the nature of the apoptotic stimulus.…”

Section: Discussionmentioning

confidence: 99%

Protective role of retinoid X receptor in H9c2 cardiomyocytes from hypoxia/reoxygenation injury in rats

Shan¹,

Xu²,

Huang³

et al. 2014

World Journal of Emergency Medicine

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BACKGROUND: Retinoid X receptor (RXR) plays a central role in the regulation of intracellular receptor signaling pathways. The activation of RXR has protective effect on H 2 O 2 -induced apoptosis of H9c2 ventricular cells in rats. But the protective effect and mechanism of activating RXR in cardiomyocytes against hypoxia/reoxygenation (H/R)-induced oxidative iniury are still unclear. METHODS:The model of H/R injury was established through hypoxia for 2 hours and reoxygenation for 4 hours in H9c2 cardiomyocytes of rats. 9-cis-retinoic acid (9-cis RA) was obtained as an RXR agonist, and HX531 as an RXR antagonist. Cultured cardiomyocytes were randomly divided into four groups: sham group, H/R group, H/R+9-cis RA -pretreated group (100 nmol/L 9-cis RA), and H/R+9-cis RA+HX531-pretreated group (2.5 μmol/L HX531). The cell viability was measured by MTT, apoptosis rate of cardiomyocytes by flow cytometry analysis, and mitochondrial membrane potential (ΔΨm) by JC-1 fluorescent probe, and protein expressions of Bcl-2, Bax and cleaved caspase-9 with Western blotting. All measurement data were expressed as mean±standard deviation, and analyzed using one-way ANOVA and the Dunnett test. Differences were considered signifi cant when P was <0.05. RESULTS:Pretreatment with RXR agonist enhanced cell viability, reduced apoptosis ratio, and stabled ΔΨm. Dot blotting experiments showed that under H/R stress conditions, Bcl-2 protein level decreased, while Bax and cleaved caspase-9 were increased. 9-cis RA administration before H/R stress prevented these effects, but the protective effects of activating RXR on cardiomyocytes against H/R induced oxidative injury were abolished when pretreated with RXR pan-antagonist HX531. CONCLUSION:The activation of RXR has protective effects against H/R injury in H9c2 cardiomyocytes of rats through attenuating signaling pathway of mitochondria apoptosis.

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Section: Discussionmentioning

confidence: 99%

Protective role of retinoid X receptor in H9c2 cardiomyocytes from hypoxia/reoxygenation injury in rats

Shan¹,

Xu²,

Huang³

et al. 2014

World Journal of Emergency Medicine

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“…Human mesangial cells (HMCs) were obtained from adult kidney tissue, as we have previously described, and were used between passages 8 and 12 (28). An immortalized human mesangial cell line (HMCL) was developed by Professor J. D. Sraer (Hôpital Tenon, Paris, France) (41) and is a kind gift from Dr. Xiongzhong Ruan (Royal Free and University College Medical School, London, UK) (35).…”

Section: Methodsmentioning

confidence: 99%

In vitro models of TGF-β-induced fibrosis suitable for high-throughput screening of antifibrotic agents

Norman²,

Shrivastav³

et al. 2007

American Journal of Physiology-Renal Physiology

111

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Progressive fibrosis is a cause of progressive organ dysfunction. Lack of quantitative in vitro models of fibrosis accounts, at least partially, for the slow progress in developing effective antifibrotic drugs. Here, we report two complementary in vitro models of fibrosis suitable for high-throughput screening. We found that, in mesangial cells and renal fibroblasts grown in eight-well chamber slides, transforming growth factor-β1 (TGF-β1) disrupted the cell monolayer and induced cell migration into nodules in a dose-, time- and Smad3-dependent manner. The nodules contained increased interstitial collagens and showed an increased collagen I:IV ratio. Nodules are likely a biological consequence of TGF-β1-induced matrix overexpression since they were mimicked by addition of collagen I to the cell culture medium. TGF-β1-induced nodule formation was inhibited by vacuum ionized gas treatment of the plate surface. This blockage was further enhanced by precoating plates with matrix proteins but was prevented, at least in part, by poly-l-lysine (PLL). We have established two cell-based models of TGF-β-induced fibrogenesis, using mesangial cells or fibroblasts cultured in matrix protein or PLL-coated 96-well plates, on which TGF-β1-induced two-dimensional matrix accumulation, three-dimensional nodule formation, and monolayer disruption can be quantitated either spectrophotometrically or by using a colony counter, respectively. As a proof of principle, chemical inhibitors of Alk5 and the antifibrotic compound tranilast were shown to have inhibitory activities in both assays.

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“…Antihypertrophic effect of retinoic acid-mediated signaling has been demonstrated in myocardial cells in response to angiotensin II, endothelin-1, and phenylephrine (28,29). Retinoic acid functions by binding to nuclear receptor proteins, the retinoic acid receptor (RAR), and the retinoid X receptor (RXR) family, which are expressed in a variety of cell types and act as transcription factors upon ligand binding (30,31). Previous studies have shown that retinoic acid receptors also interact with other transcription factors to mediate gene expression (32,33).…”

Section: Atrial Natriuretic Peptide (Anp)mentioning

confidence: 99%

Interactive Roles of Ets-1, Sp1, and Acetylated Histones in the Retinoic Acid-dependent Activation of Guanylyl Cyclase/Atrial Natriuretic Peptide Receptor-A Gene Transcription

Kumar

Garg

Bolden

et al. 2010

Journal of Biological Chemistry

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Cardiac hormones atrial and brain natriuretic peptides activate guanylyl cyclase/natriuretic peptide receptor-A (GC-A/ NPRA), which plays a critical role in reduction of blood pressure and blood volume. Currently, the mechanisms responsible for regulating the Npr1 gene (coding for GC-A/NPRA) transcription are not well understood. The present study was conducted to examine the interactive roles of all-trans retinoic acid (ATRA), Ets-1, Sp1, and histone acetylation on the transcriptional regulation and function of the Npr1 gene. Deletion analysis of the Npr1 promoter and luciferase assays showed that ATRA enhanced a 16-fold Npr1 promoter activity and greatly stimulated guanylyl cyclase (GC) activity of the receptor protein in both atrial natriuretic peptide (ANP)-dependent and -independent manner. As confirmed by gel shift and chromatin immunoprecipitation assays, ATRA enhanced the binding of both Ets-1 and Sp1 to the Npr1 promoter. The retinoic acid receptor ␣ (RAR␣) was recruited by Ets-1 and Sp1 to form a transcriptional activator complex with their binding sites in the Npr1 promoter. Interestingly, ATRA also increased the acetylation of histones H3 and H4 and enhanced their recruitment to Ets-1 and Sp1 binding sites within the Npr1 promoter. Collectively, the present results demonstrate that ATRA regulates Npr1 gene transcription and GC activity of the receptor by involving the interactive actions of Ets-1, Sp1, and histone acetylation. Atrial natriuretic peptide (ANP)2 is a circulatory hormone, which plays a pivotal role in the regulation of sodium excretion, fluid volume, steroidogenesis, and cell proliferation, important factors in the control of blood pressure and blood volume (1-4). One of the principal loci involved in the regulatory actions of ANP is the guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), which produces the intracellular second messenger cGMP, thus plays a central role in the pathophysiology of hypertension and cardiovascular disorders (4 -7). The signaling of ANP/cGMP through its downstream effector proteins, including cGMP-dependent protein kinases, phosphodiesterases, and cyclic nucleotide-gated ion channels, mediates the cellular effects of NPRA (4, 8). Gene-targeting and expression studies of Npr1 (coding for GC-A/NPRA) have identified the hallmark significance of this receptor in protecting against renal and cardiac pathophysiological conditions such as inhibiting the cardiac hypertrophic growth and fibrosis, extracellular matrix remodeling, and cell proliferation (9 -13). Earlier studies have demonstrated a significant association of Npr1 gene variants with hypertensive family history, left ventricular mass index, and left ventricular septal wall thickness in human essential hypertension (14, 15). It has also been shown that a longer thymine adenine repeat unit in spontaneously hypertensive rats regulates the transcription of the Npr1 gene, thus affecting diastolic blood pressure (16). Little is known about transcriptional regulation of the Npr1 gene, but the activity an...

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Human renal mesangial cells are a target for the anti‐inflammatory action of 9‐cis retinoic acid

Cited by 32 publications

References 56 publications

Protective role of retinoid X receptor in H9c2 cardiomyocytes from hypoxia/reoxygenation injury in rats

Protective role of retinoid X receptor in H9c2 cardiomyocytes from hypoxia/reoxygenation injury in rats

In vitro models of TGF-β-induced fibrosis suitable for high-throughput screening of antifibrotic agents

Interactive Roles of Ets-1, Sp1, and Acetylated Histones in the Retinoic Acid-dependent Activation of Guanylyl Cyclase/Atrial Natriuretic Peptide Receptor-A Gene Transcription

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