Piperlongumine Attenuates High Calcium/Phosphate-Induced Arterial Calcification by Preserving P53/PTEN Signaling

Shi, Wenxiang; Lu, Jiuwei; Li, Junhan; Qiu, Ming; Lü, Yan; Gu, Jia; Kong, Xiangqing; Sun, Wei

doi:10.3389/fcvm.2020.625215

Cited by 13 publications

(9 citation statements)

References 40 publications

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“…In contrast to our data, recent studies have reported reduced expression of p53 during VSMC calcification following treatment of cells with the putative cancer therapeutics, piperlongumine [ 50 ] and teniposide [ 51 ]. These divergent observations may reflect key differences in the species, passage status and culture conditions of the cells investigated.…”

Section: Discussioncontrasting

confidence: 99%

“…These divergent observations may reflect key differences in the species, passage status and culture conditions of the cells investigated. Furthermore, these findings likely reflect the activation of different signalling mechanisms, with piperlongumine modulating PTEN transcription [ 50 ] and teniposide regulating the miR-203-3p-BMP2 pathway [ 51 ]. Indeed, our data support novel findings challenging the commonly accepted paradigm of p53 having primarily pro-apoptotic functions in VSMCs [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

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p53 Regulates Mitochondrial Dynamics in Vascular Smooth Muscle Cell Calcification

Phadwal

Tang

Luijten

et al. 2023

IJMS

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Arterial calcification is an important characteristic of cardiovascular disease. It has key parallels with skeletal mineralization; however, the underlying cellular mechanisms responsible are not fully understood. Mitochondrial dynamics regulate both bone and vascular function. In this study, we therefore examined mitochondrial function in vascular smooth muscle cell (VSMC) calcification. Phosphate (Pi)-induced VSMC calcification was associated with elongated mitochondria (1.6-fold increase, p < 0.001), increased mitochondrial reactive oxygen species (ROS) production (1.83-fold increase, p < 0.001) and reduced mitophagy (9.6-fold decrease, p < 0.01). An increase in protein expression of optic atrophy protein 1 (OPA1; 2.1-fold increase, p < 0.05) and a converse decrease in expression of dynamin-related protein 1 (DRP1; 1.5-fold decrease, p < 0.05), two crucial proteins required for the mitochondrial fusion and fission process, respectively, were noted. Furthermore, the phosphorylation of DRP1 Ser637 was increased in the cytoplasm of calcified VSMCs (5.50-fold increase), suppressing mitochondrial translocation of DRP1. Additionally, calcified VSMCs showed enhanced expression of p53 (2.5-fold increase, p < 0.05) and β-galactosidase activity (1.8-fold increase, p < 0.001), the cellular senescence markers. siRNA-mediated p53 knockdown reduced calcium deposition (8.1-fold decrease, p < 0.01), mitochondrial length (3.0-fold decrease, p < 0.001) and β-galactosidase activity (2.6-fold decrease, p < 0.001), with concomitant mitophagy induction (3.1-fold increase, p < 0.05). Reduced OPA1 (4.1-fold decrease, p < 0.05) and increased DRP1 protein expression (2.6-fold increase, p < 0.05) with decreased phosphorylation of DRP1 Ser637 (3.20-fold decrease, p < 0.001) was also observed upon p53 knockdown in calcifying VSMCs. In summary, we demonstrate that VSMC calcification promotes notable mitochondrial elongation and cellular senescence via DRP1 phosphorylation. Furthermore, our work indicates that p53-induced mitochondrial fusion underpins cellular senescence by reducing mitochondrial function.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

p53 Regulates Mitochondrial Dynamics in Vascular Smooth Muscle Cell Calcification

Phadwal

Tang

Luijten

et al. 2023

IJMS

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“…After 24 to 48 hours, the growing medium was replaced with the CaP medium including DMEM medium, 5% FBS, 100 U/mL penicillin, 100 μg/mL streptomycin, 1.5 mM calcium, and 2.0 mM phosphate for a further 2 to 3 days incubation to induce the calcification of VSMCs. 34 In the other calcification model, the osteogenic calcification medium (OGM) consisted of high glucose DMEM medium, 10% FBS, 100 U/mL penicillin, 100 μg/mL streptomycin, 0.1 μmol/L dexamethasone, 50 μg/mL ascorbic acid, 5 mmol/L β‐glycerophosphate, 4 mmol/L CaCl 2 , and 1 μmol/L insulin. The medium was changed every 3 days for 14 to 17 days to induce calcium deposition in the RVSMCs.…”

Section: Methodsmentioning

confidence: 99%

“…Mice (n=10) were intraperitoneally injected with vitamin D 3 (400 000 IU/kg per day; Sigma) dissolved in olive oil for 14 consecutive days, and the same volume olive oil injection was used as a control. 34 The body weight of mice was recorded every 3 days during the experiment period. At day 28, mice aortas were removed and kept in 4% paraformaldehydesolution for further analysis.…”

Section: Methodsmentioning

confidence: 99%

Interleukin‐29 Accelerates Vascular Calcification via JAK2/STAT3/BMP2 Signaling

Hao

Zhou

Zhang

et al. 2023

JAHA

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Background Vascular calcification (VC), associated with enhanced cardiovascular morbidity and mortality, is characterized by the osteogenic transdifferentiation of vascular smooth muscle cells. Inflammation promotes VC initiation and progression. Interleukin (IL)‐29, a newly discovered member of type III interferon, has recently been implicated in the pathogenesis of autoimmune diseases. Here we evaluated the role of IL‐29 in the VC process and underlying inflammatory mechanisms. Methods and Results The mRNA expression of IL‐29 was significantly increased and positively associated with an increase in BMP2 (bone morphogenetic protein 2) mRNA level in calcified carotid arteries from patients with coronary artery disease or chronic kidney disease. IL‐29 and BMP2 proteins are colocalized in human calcified arteries. IL‐29 binding to its specific receptor IL‐28Rα (IL‐28 receptor α) (IL‐29/IL‐28Rα) inhibited the proliferation of rat vascular smooth muscle cells without altering cell apoptosis or migration. IL‐29 promoted the calcification of rat vascular smooth muscle cells and their osteogenic transdifferentiation in vitro as well as the rat aortic ring calcification ex vivo, induced by the calcification medium or osteogenic medium. The procalcification effect of IL‐29 was reduced by pharmacological inhibition of IL‐29/IL‐28Rα binding as well as suppression of janus kinase 2/signal transducer and activator of transcription pathway activation, accompanied by decreased BMP2 expression in the cultured rat vascular smooth muscle cells. Conclusions These results suggest an important role of IL‐29 in VC development, at least partly, via activating the janus kinase 2/signal transducer and activator of transcription 3 signaling. Inhibition of IL‐29 or its specific receptor, IL‐28Rα, may provide a novel strategy to reduce VC in patients with vascular diseases.

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“…Increased expression of p7056K will then induce the activation of bone morphogenetic protein 2/transforming growth factor β/Smad1/5/8 (BMP2/TGF-β/Smad1/5/8) signaling pathway manifested in increased expression of Runx2, osteocalcin (OCN), alkaline phosphatase (ALP), and osterix (Osx) thus generating pre-osteoblast differentiation into osteoblasts. [31][32][33][34][35][36][37][38][39][40][41][42][43]…”

Section: Discussionmentioning

confidence: 99%

Combination of anthocyanin ternatin and hydroxyapatite/β-tricalcium phosphate coralline as a socket preservation biomaterial in dental implant: A narrative review

Nugraha¹,

Sosiawan²,

Anwar³

et al. 2022

World J. Adv. Res. Rev.

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Background: Tooth extraction is surgical treatment with clinical manifestation is alveolar bone resorption of 11-63% which potentially fails dental implant treatment. Socket preservation is bone regeneration treatment to minimize bone morphological changes in post-extraction using bone graft. Anti-inflammatory biomaterial is needed to modulate inflammatory cascade in the lesion. Anthocyanin ternatin is a flavonoid derived from butterfly pea (Clitoria ternatea) as an anti-inflammatory and antioxidants agent. Hydroxyapatite/β-Tricalcium Phosphate coralline (HA/β-TCP coralline) is a combination of bioceramic material from calcium carbonate heating of Porites spp. coral which has potential to induce osteogenesis, osteoinduction, and osteoconduction. Combination of Anthocyanin ternatin and HA/β-TCP coralline applied to the defect area in dried powder form to induce hard tissue regeneration. Purpose: To describe the potential of combination of Anthocyanin ternatin and HA/β-TCP coralline as a socket preservation biomaterial in dental implant. Review: Combination of Anthocyanin ternatin and dried powder HA/β-TCP coraline is applied in dental socket. Anthocyanin ternatin suppresses ROS and iNOS then inhibit NF-kB signaling pathway. Downregulation of the pathway decreases TNF-α and IL-1β/6 expression so the expression of RANKL is inhibited. Lowering of ROS followed by upregulated Ca2+ level from HA/β-TCP coralline causes the increase in DKK1 and PTEN expression so Akt and Wnt expression is induced. Upregulation of the proteins induces the BMP2/TGF-β/Smad1/5/8 signaling pathway activation manifest in the increase of Runx2, OCN, and Osx then the preosteoblast differentiation to osteoblast is increased. Conclusion: Combination of Anthocyanin ternatin and HA/β-TCP coralline is potential as socket preservation biomaterial in dental implant.

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Piperlongumine Attenuates High Calcium/Phosphate-Induced Arterial Calcification by Preserving P53/PTEN Signaling

Cited by 13 publications

References 40 publications

p53 Regulates Mitochondrial Dynamics in Vascular Smooth Muscle Cell Calcification

p53 Regulates Mitochondrial Dynamics in Vascular Smooth Muscle Cell Calcification

Interleukin‐29 Accelerates Vascular Calcification via JAK2/STAT3/BMP2 Signaling

Combination of anthocyanin ternatin and hydroxyapatite/β-tricalcium phosphate coralline as a socket preservation biomaterial in dental implant: A narrative review

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