Nitric oxide regulates adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells

Mesquita, A P S; Matsuoka, M; Lopes, S A; Filho, Paulo Castanho A. Pernambuco; Cruz, Alberto Sanchez De la; Nader, Helena B.; Lopes, Carla Cristina

doi:10.1590/1414-431x2021e11612

Cited by 8 publications

(9 citation statements)

References 38 publications

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“…Our previous studies have shown that nitric oxide can inhibit MMP2 expression by inducing activating transcription factor 3 in endothelial cells (Mesquita et al, 2022). In this way, our results showed the important relationship between the expression of MMP2 and SDC4.…”

Section: Effect Of Sdc4 Silencing On Nitric Oxide (No) Production And...supporting

confidence: 77%

“…SDC4 silencing can decrease NO production in anoikis‐resistant endothelial cells, observed by the Griess reaction assay and by increased levels of phosphorylation of the inhibition site (Thr495) and decrease of the activation site (Ser1177). Our previous studies have shown that nitric oxide can inhibit MMP2 expression by inducing activating transcription factor 3 in endothelial cells (Mesquita et al, 2022). In this way, our results showed the important relationship between the expression of MMP2 and SDC4.…”

Section: Discussionmentioning

confidence: 98%

“…After 24 h, the culture medium was replaced with F‐12 medium. The culture medium was collected and levels of NO 2 ‐ /NO 3 ‐ were determined by the Griess reaction using a commercial kit from Cayman Chemical Co. (cat# 780001) as previously described (Mesquita et al, 2022). The azo dye formed as a product of Griess diazotization reaction was spectrophotometrically quantitated based on its absorbance at 570 nm, using a microplate reader DR‐200B‐NM (Kazuaki) The released nitrite values were calculated based on a NaNO 2 standard curve.…”

Section: Methodsmentioning

confidence: 99%

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Effects of syndecan‐4 silencing on the extracellular matrix remodeling in anoikis‐resistant endothelial cells

Onyeisi,

Nader,

Lopes

2024

Cell Biology International

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Anoikis is a process of programmed cell death induced by the loss of cell/matrix interactions. In previous work, we have shown that the acquisition of anoikis resistance upregulates syndecan‐4 (SDC4) expression in endothelial cells. In addition, SDC4 gene silencing by microRNA interference reverses the transformed phenotype of anoikis‐resistant endothelial cells. Due to this role of SDC4 in regulating the behavior of anoikis‐resistant endothelial cells, we have evaluated that the functional consequences of SDC4 silencing in the extracellular matrix (ECM) remodeling in anoikis‐resistant rabbit aortic endothelial cells submitted to SDC4 gene silencing (miR‐Syn4‐Adh‐1‐EC). For this, we evaluated the expression of adhesive proteins, ECM receptors, nonreceptor protein‐tyrosine kinases, and ECM‐degrading enzymes and their inhibitors. Altered cell behavior was monitored by adhesion, migration, and tube formation assays. We found that SDC4 silencing led to a decrease in migration and angiogenic capacity of anoikis‐resistant endothelial cells; this was accompanied by an increase in adhesion to fibronectin. Furthermore, after SDC4 silencing, we observed an increase in the expression of fibronectin, collagen IV, and vitronectin, and a decrease in the expression of integrin α5β1 and αvβ3, besides that, silenced cells show an increase in Src and FAK expression. Quantitative polymerase chain reaction and Western blot analysis demonstrated that SDC4 silencing leads to altered gene and protein expression of MMP2, MMP9, and HSPE. Compared with parental cells, SDC4 silenced cells showed a decrease in nitric oxide production and eNOS expression. In conclusion, these data demonstrate that SDC4 plays an important role in ECM remodeling. In addition, our findings represent an important step toward understanding the mechanism by which SDC4 can reverse the transformed phenotype of anoikis‐resistant endothelial cells.

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Section: Effect Of Sdc4 Silencing On Nitric Oxide (No) Production And...supporting

confidence: 77%

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

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Effects of syndecan‐4 silencing on the extracellular matrix remodeling in anoikis‐resistant endothelial cells

Onyeisi,

Nader,

Lopes

2024

Cell Biology International

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“…ROS in general and superoxide specifically have been shown to promote cell migration in multiple other contexts [74][75][76], which suggests the possibility that in planarians WMF effects might potentially include changes in ROS-mediated cell migration. However, since superoxide regulation of cell migration has commonly been shown to occur via SOD-induced increases in H 2 O 2 signaling [77,78], and since RNS signaling has been shown to be a negative regulator of cell migration [79,80], this area of inquiry would require a great deal more investigation.…”

Section: Discussionmentioning

confidence: 99%

Weak magnetic fields modulate superoxide to control planarian regeneration

2023

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Reactive oxygen species (ROS) signaling regulates cell behaviors and tissue growth in development, regeneration, and cancer. Commonly, ROS are modulated pharmacologically, which while effective comes with potential complications such as off-target effects and lack of drug tolerance. Thus, additional non-invasive therapeutic methods are necessary. Recent advances have highlighted the use of weak magnetic fields (WMFs, <1 mT) as one promising approach. We previously showed that 200 μT WMFs inhibit ROS formation and block planarian regeneration. However, WMF research in different model systems at various field strengths have produced a range of results that do not fit common dose response curves, making it unclear if WMF effects are predictable. Here, we test hypotheses based on spin state theory and the radical pair mechanism, which outlines how magnetic fields can alter the formation of radical pairs by changing electron spin states. This mechanism suggests that across a broad range of field strengths (0–900 μT) some WMF exposures should be able to inhibit while others promote ROS formation in a binary fashion. Our data reveal that WMFs can be used for directed manipulation of stem cell proliferation, differentiation, and tissue growth in predictable ways for both loss and gain of function during regenerative growth. Furthermore, we examine two of the most common ROS signaling effectors, hydrogen peroxide and superoxide, to begin the identification and elucidation of the specific molecular targets by which WMFs affect tissue growth. Together, our data reveal that the cellular effects of WMF exposure are highly dependent on ROS, and we identify superoxide as a specific ROS being modulated. Altogether, these data highlight the possibilities of using WMF exposures to control ROS signaling in vivo and represent an exciting new area of research.

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“…These findings indicate that TIMP3 plays an antiapoptotic role by inhibiting the expression of MMP‐2 and MMP‐7, as well as the activity of MMP‐2. According to previous reports, MMPs can induce apoptosis through anoikis and the activation of FasL, suggesting that multiple molecular mechanisms may contribute to photoreceptor apoptosis caused by MMP‐2 and MMP‐7 [41,67–70].…”

Section: Discussionmentioning

confidence: 99%

NDRG2 alleviates photoreceptor apoptosis by regulating the STAT3/TIMP3/MMP pathway in mice with retinal degenerative disease

Chen,

Xiong,

Deng

et al. 2023

The FEBS Journal

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Photoreceptor apoptosis is the main pathological feature of retinal degenerative diseases; however, the underlying molecular mechanism has not been elucidated. Recent studies have shown that N‐myc downstream regulated gene 2 (NDRG2) exerts a neuroprotective effect on the brain and spinal cord. In addition, our previous studies have confirmed that NDRG2 is expressed in mouse retinal photoreceptors and counteracts N‐methyl‐N‐nitrosourea (MNU)‐induced apoptosis. However, the underlying molecular mechanism remains unclear. In this study, we observed that the expression of NDRG2 was not only significantly inhibited in photoreceptors after MNU treatment but also after hydrogen peroxide treatment, and photoreceptor apoptosis was alleviated or aggravated after overexpression or knockdown of NDRG2 in the 661W photoreceptor cell line, respectively. The apoptosis inhibitor Z‐VAD‐FMK rescued photoreceptor apoptosis induced by MNU after NDRG2 knockdown. Next, we screened and identified tissue inhibitor of metalloproteinases 3 (TIMP3) as the downstream molecule of NDRG2 in 661W cells by using quantitative real‐time polymerase chain reaction. TIMP3 exerts a neuroprotective effect by inhibiting the expression of matrix metalloproteinases (MMPs). Subsequently, we found that signal transducer and activator of transcription 3 (STAT3) mediated the NDRG2‐associated regulation of TIMP3. Finally, we overexpressed NDRG2 in mouse retinal tissues by intravitreally injecting an adeno‐associated virus with mouse NDRG2 in vivo. Results showed that NDRG2 upregulated the expression of phospho‐STAT3 (p‐STAT3) and TIMP3, while suppressing MNU‐induced photoreceptor apoptosis and MMP expression. Our findings revealed how NDRG2 regulates the STAT3/TIMP3/MMP pathway and uncovered the molecular mechanism underlying its neuroprotective effect on mouse retinal photoreceptors.

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Nitric oxide regulates adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells

Cited by 8 publications

References 38 publications

Effects of syndecan‐4 silencing on the extracellular matrix remodeling in anoikis‐resistant endothelial cells

Effects of syndecan‐4 silencing on the extracellular matrix remodeling in anoikis‐resistant endothelial cells

Weak magnetic fields modulate superoxide to control planarian regeneration

NDRG2 alleviates photoreceptor apoptosis by regulating the STAT3/TIMP3/MMP pathway in mice with retinal degenerative disease

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