A novel CD147 inhibitor, SP-8356, reduces neointimal hyperplasia and arterial stiffness in a rat model of partial carotid artery ligation

Pahk, Kisoo; Noh, Hyojin; Joung, Chanmin; Jang, Mi; Song, Hoyoung; Kim, Kyung Won; Han, Ki-Hoon; Hwang, Jong Ik; Kim, Sungeun; Kim, Won Ki

doi:10.1186/s12967-019-2024-y

Cited by 22 publications

(19 citation statements)

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“…CD147 homophilic interactions, such as dimerization and CD147-CypA interactions, are the two dominant mechanisms leading to MMP-9 upregulation [16]. Accumulated evidence from our previous [20] and current studies suggests that SP-8356 can synergistically inhibit MMP-9 activity by binding to CD147 and simultaneously attenuating CD147 dimerization and CD147-CypA interactions. However, detailed basic mechanisms require further investigation.…”

Section: Discussionmentioning

confidence: 59%

“…SP-8356((1S,5R)-4-(3,4-dihydroxy-5-methoxystyryl)-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-one), a novel synthetic small-molecule drug, is a (1S)-(−)-verbenone derivative with anti-inflammatory and anti-oxidative activities ( Figure 1A) [19]. In addition, we recently found that SP-8356 binds to CD147 and reduces neointimal hyperplasia through inhibition of MMP-9 activity [20]. We also found that SP-8356 has an anti-tumor effect through inhibition of CD147/MMP-9 pathway [21].…”

Section: Introductionmentioning

confidence: 99%

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SP-8356, a Novel Inhibitor of CD147-Cyclophilin A Interactions, Reduces Plaque Progression and Stabilizes Vulnerable Plaques in apoE-Deficient Mice

Pahk

Joung

Song

et al. 2019

IJMS

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Interactions between CD147 and cyclophilin A (CypA) promote plaque rupture that causes atherosclerosis-related cardiovascular events, such as myocardial infarction and stroke. Here, we investigated whether SP-8356 ((1S,5R)-4-(3,4-dihydroxy-5-methoxystyryl)-6, 6-dimethylbicyclo[3.1.1]hept-3-en-2-one), a novel drug, can exert therapeutic effects against plaque progression and instability through disruption of CD147-CypA interactions in apolipoprotein E-deficient (ApoE KO) mice. Immunocytochemistry and immunoprecipitation analyses were performed to assess the effects of SP-8356 on CD147-CypA interactions. Advanced plaques were induced in ApoE KO mice via partial ligation of the right carotid artery coupled with an atherogenic diet, and SP-8356 (50 mg/kg) orally administrated daily one day after carotid artery ligation for three weeks. The anti-atherosclerotic effect of SP-8356 was assessed using histological and molecular approaches. SP-8356 interfered with CD147-CypA interactions and attenuated matrix metalloproteinase-9 activation. Moreover, SP-8356 induced a decreased in atherosclerotic plaque size in ApoE KO mice and stabilized plaque vulnerability by reducing the necrotic lipid core, suppressing macrophage infiltration, and enhancing fibrous cap thickness through increasing the content of vascular smooth muscle cells. SP-8356 exerts remarkable anti-atherosclerotic effects by suppressing plaque development and improving plaque stability through inhibiting CD147-CypA interactions. Our novel findings support the potential utility of SP-8356 as a therapeutic agent for atherosclerotic plaque.Keywords: atherosclerosis; plaque; plaque vulnerability; cluster of differentiation 147 (CD147); matrix metalloproteinase; matrix metalloproteinase-9 (MMP-9) Int.

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

SP-8356, a Novel Inhibitor of CD147-Cyclophilin A Interactions, Reduces Plaque Progression and Stabilizes Vulnerable Plaques in apoE-Deficient Mice

Pahk

Joung

Song

et al. 2019

IJMS

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“…One possible mechanism is that CD147 can serve as both receptor and ligand for adjacent CD147, which is called the homophilic interaction such as dimerization [13,31,32]. Recently, we found that SP-8356 shows a high binding affinity with CD147 and directly inhibits CD147 dimerization [14]. Thus, the inhibitory effect of SP-8356 on CD147 dimerization may contribute to its anti-fibrotic effect in the alkali-burned cornea.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we reported that a novel synthetic small-molecule drug SP-8356 ((1S,5R)-4-(3,4-dihydroxy-5-methoxystyryl)-6,6-dimethylbicyclo[3.1.1] hept-3-en-2-one) directly binds to CD147 thereby inhibiting neointimal hyperplasia and stabilizing plaque vulnerability in animal models through the inhibition of MMP-9 activity [14,15] . Furthermore, we also found that SP-8356 possesses anti-tumor effect through the inhibition of CD147/MMP-9 pathway [16].…”

Section: Introductionmentioning

confidence: 99%

A Novel CD147 Inhibitor, SP-8356, Attenuates Pathological Fibrosis in Alkali-Burned Rat Cornea

Joung

Noh

Jung

et al. 2020

IJMS

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The corneal fibrotic responses to corneal damage often lead to severe corneal opacification thereby resulting in severe visual impairment or even blindness. The persistence of corneal opacity depends heavily on the activity of corneal myofibroblast. Myofibroblasts are opaque and synthesize a disorganized extracellular matrix (ECM) and thus promoting opacification. Cluster of differentiation 147 (CD147), a member of the immunoglobulin superfamily, is known to play important roles in the differentiation process from fibroblast to myofibroblast in damaged cornea and may therefore be an effective target for treatment of corneal opacity. Here, we examined the therapeutic efficacy of novel CD147 inhibiting verbenone derivative SP-8356 ((1S,5R)-4-(3,4dihydroxy-5-methoxystyryl)-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-one) on corneal fibrosis. Topical SP-8356 significantly reduced corneal haze and fibrosis in the alkali-burned cornea. In detail, SP-8356 inhibited both alpha-smooth muscle actin (α-SMA) expressing myofibroblast and its ECM-related products, such as matrix-metalloproteinase-9 and collagen type III and IV. Similar to SP-8356, topical corticosteroid (prednisolone acetate, PA) also reduced the ECM-related products and opacification. However, prednisolone acetate failed to decrease the population of α-SMA-positive corneal myofibroblast. In conclusion, SP-8356 is capable enough to prevent corneal haze by preventing pathological fibrosis after severe corneal damage. Therefore, SP-8356 could be a potentially promising therapeutic drug for corneal fibrosis.

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“…Furthermore, BSG inhibitors are now being developed and tested [66][67][68], and we hope our study can provide some evidence for BSG targeted treatment of TC.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Basigin Expression Level in Thyroid Cancer Tissues

Guo

Tang

Pang

et al. 2020

Preprint

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Background: Thyroid cancer (TC) is the most common endocrine malignancy, Basigin (also known as BSG) plays a crucial role in tumor cell invasion, metastasis, and angiogenesis. This study was designed to identify the change of BSG expression in TC and its possible potential mechanism. Methods: The BSG expression levels in TC were demonstrated using data collected from in-house immunohistochemical (IHC), RNA-sequencing (RNA-seq), microarrays and literatures. Integrated analysis was performed to determined BSG expression levels in TC comprehensively. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed with the integration of BSG co-expressed genes and differentially expressed genes (DEGs) in TC tissues to explore the potential mechanisms of BSG in TC. Results: The protein expression level of BSG was significantly higher in TC cases based on the IHC experiments. In addition, the combined SMD for BSG expression was 0.39 (p<0.0001), the diagnostic odds ratio was 3.69, and the AUC of the sROC curve was 0.6986 using 1182 TC cases and 437 non-cancerous cases from 17 independent datasets. Furthermore, BSG co-expressed genes tended to be enriched in gene terms of the extracellular matrix (ECM), cell adhesion, and cell-cell interactions. The expression levels of nine hub BSG co-expressed genes were markedly up-regulated in TC cases. Conclusion: BSG expression levels were closely correlated with the progression of TC and may affect the signals of the ECM, cell adhesion, and cell-cell interactions.

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A novel CD147 inhibitor, SP-8356, reduces neointimal hyperplasia and arterial stiffness in a rat model of partial carotid artery ligation

Cited by 22 publications

References 50 publications

SP-8356, a Novel Inhibitor of CD147-Cyclophilin A Interactions, Reduces Plaque Progression and Stabilizes Vulnerable Plaques in apoE-Deficient Mice

SP-8356, a Novel Inhibitor of CD147-Cyclophilin A Interactions, Reduces Plaque Progression and Stabilizes Vulnerable Plaques in apoE-Deficient Mice

A Novel CD147 Inhibitor, SP-8356, Attenuates Pathological Fibrosis in Alkali-Burned Rat Cornea

Immunohistochemical Basigin Expression Level in Thyroid Cancer Tissues

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