Sphingosine-1-Phosphate Signaling in Cardiovascular Diseases

Wang, Na; Li, Jingyi; Zeng, Bo; Chen, Guilan

doi:10.3390/biom13050818

Cited by 16 publications

(3 citation statements)

References 116 publications

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“…Recently, SphK1 was found to influence S1P upregulation more than SphK2, and S1PR3 was linked to fibrotic manifestations in the lung [44]. Wang et al, 2023, reported that abnormal S1P content in the circulation affected cardiovascular disorder pathogenesis and S1PR3 mediation of cell proliferation and vascular permeability [45]. Furthermore, the S1PR3 antagonist was observed to improve graft viability in rat heart transplants [102].…”

Section: Discussionmentioning

confidence: 99%

“…Sphingosine 1-phosphate (S1P) is a pleiotropic bioactive lipid mediator that is formed from the catalysis of sphingosine kinases (SphK1 and SphK2). Sphingolipids (SPLs), such as S1P, bind to S1P receptors (S1PR1-5), inducing various cellular responses, and have been implicated in many studies as key regulators of fibrosis in various tissues and organs [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ], including the cornea [ 26 , 33 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ].…”

Section: Introductionmentioning

confidence: 99%

“…In the cornea, the cross-talks between TGF-β and S1P signaling remain elusive; however, studies in other tissues suggest that TGF-β induces the activity of sphingosine kinase [ 45 , 57 ]. Several recent studies have demonstrated the fibrotic protective effects of TGF-β and S1P inhibition [ 58 , 59 , 60 , 61 , 62 ].…”

Section: Introductionmentioning

confidence: 99%

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Amelioration of Fibrosis via S1P Inhibition Is Regulated by Inactivation of TGF-β and SPL Pathways in the Human Cornea

Nicholas,

Basu,

Mandal

et al. 2024

IJMS

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Human corneal fibrosis can lead to opacity and ultimately partial or complete vision loss. Currently, corneal transplantation is the only treatment for severe corneal fibrosis and comes with the risk of rejection and donor shortages. Sphingolipids (SPLs) are known to modulate fibrosis in various tissues and organs, including the cornea. We previously reported that SPLs are tightly related to both, transforming growth factor beta (TGF-β) signaling and corneal fibrogenesis. The aim of this study was to investigate the effects of sphingosine-1-phosphate (S1P) and S1P inhibition on specific TGF-β and SPL family members in corneal fibrosis. Healthy human corneal fibroblasts (HCFs) were isolated and cultured in EMEM + FBS + VitC (construct medium) on 3D transwells for 4 weeks. The following treatments were prepared in a construct medium: 0.1 ng/mL TGF-β1 (β1), 1 μM sphingosine-1-phosphate (S1P), and 5 μM Sphingosine kinase inhibitor 2 (I2). Five groups were tested: (1) control (no treatment); rescue groups; (2) β1/S1P; (3) β1/I2; prevention groups; (4) S1P/β1; and (5) I2/β1. Each treatment was administered for 2 weeks with one treatment and switched to another for 2 weeks. Using Western blot analysis, the 3D constructs were examined for the expression of fibrotic markers, SPL, and TGF-β signaling pathway members. Scratch assays from 2D cultures were also utilized to evaluate cell migration We observed reduced fibrotic expression and inactivation of latent TGF-β binding proteins (LTBPs), TGF-β receptors, Suppressor of Mothers Against Decapentaplegic homologs (SMADs), and SPL signaling following treatment with I2 prevention and rescue compared to S1P prevention and rescue, respectively. Furthermore, we observed increased cell migration following stimulation with I2 prevention and rescue groups, with decreased cell migration following stimulation with S1P prevention and rescue groups after 12 h and 18 h post-scratch. We have demonstrated that I2 treatment reduced fibrosis and modulated the inactivation of LTBPs, TGF-β receptors, SPLs, and the canonical downstream SMAD pathway. Further investigations are warranted in order to fully uncover the potential of utilizing SphK I2 as a novel therapy for corneal fibrosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Amelioration of Fibrosis via S1P Inhibition Is Regulated by Inactivation of TGF-β and SPL Pathways in the Human Cornea

Nicholas,

Basu,

Mandal

et al. 2024

IJMS

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Chlorogenic acid attenuates cardiac hypertrophy via up‐regulating Sphingosine‐1‐phosphate receptor1 to inhibit endoplasmic reticulum stress

Ping,

Yang,

Ning

et al. 2024

ESC Heart Failure

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AimsCardiac hypertrophy, an adaptive response of the heart to stress overload, is closely associated with heart failure and sudden cardiac death. This study aimed to investigate the therapeutic effects of chlorogenic acid (CGA) on cardiac hypertrophy and elucidate the underlying mechanisms.Methods and resultsTo simulate cardiac hypertrophy, myocardial cells were exposed to isoproterenol (ISO, 10 μM). A rat model of ISO‐induced cardiac hypertrophy was also established. The expression levels of cardiac hypertrophy markers, endoplasmic reticulum stress (ERS) markers, and apoptosis markers were measured using quantitative reverse transcription PCR and western blotting. The apoptosis level, size of myocardial cells, and heart tissue pathological changes were determined by terminal deoxynucleotidyl transferase dUTP nick‐end labelling staining, immunofluorescence staining, haematoxylin and eosin staining, and Masson's staining. We found that CGA treatment decreased the size of ISO‐treated H9c2 cells. Moreover, CGA inhibited ISO‐induced up‐regulation of cardiac hypertrophy markers (atrial natriuretic peptide, brain natriuretic peptide, and β‐myosin heavy chain), ERS markers (C/EBP homologous protein, glucose regulatory protein 78, and protein kinase R‐like endoplasmic reticulum kinase), and apoptosis markers (bax and cleaved caspase‐12/9/3) but increased the expression of anti‐apoptosis marker bcl‐2 in a dose‐dependent way (0, 10, 50, and 100 μM). Knockdown of sphingosine‐1‐phosphate receptor 1 (S1pr1) reversed the protective effect of CGA on cardiac hypertrophy, ERS, and apoptosis in vitro (P < 0.05). CGA also restored ISO‐induced inhibition on the AMP‐activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signalling in H9c2 cells, while S1pr1 knockdown abolished these CGA‐induced effects (P < 0.05). CGA (90 mg/kg/day, for six consecutive days) protected rats against cardiac hypertrophy in vivo (P < 0.05).ConclusionsCGA treatment attenuated ISO‐induced ERS and cardiac hypertrophy by activating the AMPK/SIRT1 pathway via modulation of S1pr1.

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Targeting the Sphingosine-1-Phosphate Pathway: New Opportunities in Inflammatory Bowel Disease Management

Kitsou,

Kokkotis,

Rivera‑Nieves

et al. 2024

Drugs

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Sphingosine-1-Phosphate Signaling in Cardiovascular Diseases

Cited by 16 publications

References 116 publications

Amelioration of Fibrosis via S1P Inhibition Is Regulated by Inactivation of TGF-β and SPL Pathways in the Human Cornea

Amelioration of Fibrosis via S1P Inhibition Is Regulated by Inactivation of TGF-β and SPL Pathways in the Human Cornea

Chlorogenic acid attenuates cardiac hypertrophy via up‐regulating Sphingosine‐1‐phosphate receptor1 to inhibit endoplasmic reticulum stress

Targeting the Sphingosine-1-Phosphate Pathway: New Opportunities in Inflammatory Bowel Disease Management

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