Nitric oxide modulates expression of extracellular matrix genes linked to fibrosis in kidney mesangial cells

Wani, Javid; Carl, Marina; Henger, Anna; Nelson, Peter J.; Rupprecht, Harald

doi:10.1515/bc.2007.056

Cited by 25 publications

(23 citation statements)

References 39 publications

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“…Exogenous NO-treated kidney mesangial cells decreased TSP1 mRNA (40). Treatment of human umbilical chord endothelial cells with DETANO demonstrated suppression of secreted TSP1, and this effect was independent of sGC activation and ERK phosphorylation (41).…”

Section: Tsp2 Deficiency Rescues the Enos-ko Phenotype In Ischemia Andmentioning

confidence: 87%

“…Our studies suggest that NO may influence ECM assembly and ultrastructure, which has not been described before. Previous studies in cultured mesangial cells showed that either NO stimulated through iNOS induction or exogenous GSNO altered levels of ECM molecules, including decreased collagen (type 1α1 and type 1α2), fibronectin, and TSP1, and increased laminin (40,44). The participation of NO in ECM synthesis was also demonstrated in an anti-Thy1-induced kidney damage model, where treatment with a phosphodiesterase 5 (PDE5) inhibitor, a cGMP catabolizing enzyme, displayed decreased collagen IV, fibronectin, and TSP1 (45).…”

Section: Tsp2 Deficiency Rescues the Enos-ko Phenotype In Ischemia Andmentioning

confidence: 99%

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Endothelial nitric oxide synthase controls the expression of the angiogenesis inhibitor thrombospondin 2

MacLauchlan

Yu²,

Parrish³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Injury-and ischemia-induced angiogenesis is critical for tissue repair and requires nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS). We present evidence that NO induces angiogenesis by modulating the level of the angiogenesis inhibitor thrombospondin 2 (TSP2). TSP2 levels were higher than WT in eNOS KO tissues in hind-limb ischemia and cutaneous wounds. In vitro studies confirmed that NO represses TSP2 promoter activity. Moreover, double-eNOS/TSP2 KO mice were generated and found to rescue the phenotype of eNOS KO mice. Studies in mice with knock-in constitutively active or inactive eNOS on the Akt-1 KO background showed that eNOS activity correlates with TSP2 levels. Our observations of NO-mediated regulation of angiogenesis via the suppression of TSP2 expression provide a description of improved eNOS KO phenotype by means other than restoring NO signaling.wound healing | extracellular matrix | Akt | matrix metalloproteinases E ndothelial nitric oxide synthase (eNOS) and its bioactive product nitric oxide (NO) are well-established proangiogenic molecules. Endothelial-derived NO is crucial for maintenance of proper vasodilatory tone and regulation of an antiproliferative and antiapoptotic state for endothelial cells (ECs) and has essential roles in physiological angiogenesis (1-3). Pharmacological inhibition or genetic disruption of eNOS limited angiogenesis during tissue repair, resulting in delayed wound closure (2, 4). Addition of NO donors to wounds enhanced angiogenesis and accelerated healing (5-7). eNOS KO mice recovered poorly from hind-limb ischemia as a consequence of decreased angiogenesis (3,8). These mice also displayed accelerated atherosclerosis, neointimal thickening postinjury, and hypertension (1, 9). Taken together, these observations highlight the ability of eNOS-derived NO to influence vascular function.Thrombospondins (TSPs) are a small family of antiangiogenic matricellular proteins (10). TSPs enhance clearance of matrix metalloproteinase (MMP)-2 and MMP-9 (11-13) and interact with cell-surface receptors, including α v β 3 , very low density lipoprotein receptor (VLDLR), CD36, and CD47, to inhibit angiogenesis (14). Further, ultrastructural studies demonstrated that TSP2 influences ECM assembly (15, 16). TSP2 KO mice displayed improved recovery of blood flow following ischemia (17), altered foreign body response (18,19), and accelerated wound healing (16,20,21). In contrast, TSP1 KO mice displayed delayed healing because of insufficient stimulation of inflammation (13). Consistent with these observations, the expression of TSP1 and TSP2 in tissue repair was associated with the inflammatory and repair phases, respectively (13, 16). Recently, several studies linked components of the Akt-eNOS cascade with TSPs. Specifically, TSP1 has been described to blunt the ability of NO to activate soluble guanyl cyclase (sGC) (22, 23) through interactions with CD36 and CD47 during ischemia. TSP1 has also been described to diminish eNOS activity by blocking phosphorylation at S117...

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Section: Tsp2 Deficiency Rescues the Enos-ko Phenotype In Ischemia Andmentioning

confidence: 87%

Section: Tsp2 Deficiency Rescues the Enos-ko Phenotype In Ischemia Andmentioning

confidence: 99%

Endothelial nitric oxide synthase controls the expression of the angiogenesis inhibitor thrombospondin 2

MacLauchlan

Yu²,

Parrish³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Treatment of rat renal mesangial cells with the NO donor and nitrosating agent S-nitroso-l-glutathione at 500 lM resulted in decreased TSP1 mRNA expression (295). Downregulation of TSP1 mRNA was confirmed using rat and human mesangial cells treated with the more specific NO donor spermine-NONOate.…”

Section: E No Regulation Of Tsp1 Expressionmentioning

confidence: 75%

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

Roberts

Kaur

Isenberg

2017

Antioxidants & Redox Signaling

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Significance: In contrast to structural elements of the extracellular matrix, matricellular proteins appear transiently during development and injury responses, but their sustained expression can contribute to chronic disease. Through interactions with other matrix components and specific cell surface receptors, matricellular proteins regulate multiple signaling pathways, including those mediated by reactive oxygen and nitrogen species and H 2 S. Dysregulation of matricellular proteins contributes to the pathogenesis of vascular diseases and cancer. Defining the molecular mechanisms and receptors involved is revealing new therapeutic opportunities. Recent Advances: Thrombospondin-1 (TSP1) regulates NO, H 2 S, and superoxide production and signaling in several cell types. The TSP1 receptor CD47 plays a central role in inhibition of NO signaling, but other TSP1 receptors also modulate redox signaling. The matricellular protein CCN1 engages some of the same receptors to regulate redox signaling, and ADAMTS1 regulates NO signaling in Marfan syndrome. In addition to mediating matricellular protein signaling, redox signaling is emerging as an important pathway that controls the expression of several matricellular proteins. Critical Issues: Redox signaling remains unexplored for many matricellular proteins. Their interactions with multiple cellular receptors remains an obstacle to defining signaling mechanisms, but improved transgenic models could overcome this barrier. Future Directions: Therapeutics targeting the TSP1 receptor CD47 may have beneficial effects for treating cardiovascular disease and cancer and have recently entered clinical trials. Biomarkers are needed to assess their effects on redox signaling in patients and to evaluate how these contribute to their therapeutic efficacy and potential side effects. Antioxid. Redox Signal. 27, 874-911.

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“…Another report suggested that TNF- induces expression of iNOS, leading to the production and release of NO and subsequent oxidative stress in the skeletal muscles of cachectic animals [4,35]. NO has also been reported to act at the transcriptional level to suppress gene expression in rat mesangial cells under inflammatory conditions [33]. These results suggest that, in the presence of inflammation, proinflammatory cytokines increase the expression of iNOS, leading to the production and release of NO.…”

Section: Discussionmentioning

confidence: 93%

Proinflammatory Cytokines Suppress the Expression Level of Protease-Activated Receptor-2 through the Induction of iNOS in Rat Colon

Horie

Nagai

Ohkura

et al. 2009

The Journal of Veterinary Medical Science

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ABSTRACT. Protease-activated receptor (PAR)-2 plays important roles in intestinal inflammatory responses and also contributes to intestinal digestive motility. In the distal colon of a rat experimental colitis model, expression level of PAR-2 mRNA was decreased, and relaxation through PAR-2 activation was attenuated. This study shows the effects of proinflammatory cytokines on changes to PAR-2 in rat colonic smooth muscle using an organ culture method. Colonic inflammation was induced in rats by administering dextran sodium sulphate in drinking water. Organ culture of distal colonic smooth muscle layer of normal rat was performed for up to 3 days. In the experimental colitis rat, mRNA expression levels of proinflammatory cytokines such as IL-1 and TNF- increased with inflammation. After the incubation with IL-1 and TNF- for 3 days, trypsin (PAR-2 agonist)-induced relaxation was attenuated, simultaneous with suppression of PAR-2 mRNA expression. Conversely, in this preparation, mRNA expression levels of iNOS were significantly increased. When l-NMMA was added to the medium with IL-1 and TNF-, changes to PAR-2 by these cytokine recovered. Moreover, when samples were cultured with NOC-18 (slow-releasing NO donor) for 3 days, relaxation induced by trypsin and expression of PAR-2 mRNA were attenuated. These results suggest that suppression of PAR-2 expression under inflammatory conditions is at least partially induced by NO produced in the colonic muscularis externa by proinflammatory cytokines.KEY WORDS: colonic smooth muscle, inflammatory bowel disease, motility disorder, protease-activated receptor-2.

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Nitric oxide modulates expression of extracellular matrix genes linked to fibrosis in kidney mesangial cells

Cited by 25 publications

References 39 publications

Endothelial nitric oxide synthase controls the expression of the angiogenesis inhibitor thrombospondin 2

Endothelial nitric oxide synthase controls the expression of the angiogenesis inhibitor thrombospondin 2

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

Proinflammatory Cytokines Suppress the Expression Level of Protease-Activated Receptor-2 through the Induction of iNOS in Rat Colon

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