更新于：2024-09-19

SMPDL3B

更新于：2024-09-19

基本信息

别名

Acid sphingomyelinase-like phosphodiesterase 3b、ASM-like phosphodiesterase 3b、ASML3B

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简介

Lipid-modulating phosphodiesterase (PubMed:26095358). Active on the surface of macrophages and dendritic cells and strongly influences macrophage lipid composition and membrane fluidity. Acts as a negative regulator of Toll-like receptor signaling (By similarity). Has in vitro phosphodiesterase activity, but the physiological substrate is unknown (PubMed:26095358). Lacks activity with phosphocholine-containing lipids, but can cleave CDP-choline, and can release phosphate from ATP and ADP (in vitro) (By similarity).

关联

100 项与 SMPDL3B 相关的临床结果

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100 项与 SMPDL3B 相关的转化医学

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0 项与 SMPDL3B 相关的专利（医药）

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项与 SMPDL3B 相关的文献（医药）

2024-04-01·Cellular Signalling

SMPDL3B is palmitoylated and stabilized by ZDHHC5, and its silencing aggravates diabetic retinopathy of db/db mice: Activation of NLRP3/NF-κB pathway

Article

作者: Zhou, Yun ; Zhang, Jiahua ; Yue, Song ; Li, Lihua ; Chen, Jun ; Chen, Lei

Abnormal inflammation of vascular endothelial cells occurs frequently in diabetic retinopathy (DR). Sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B) is a lipid raft enzyme and plays an anti-inflammatory role in various diseases but its function in DR-related vascular endothelial dysfunction remains unknown. We first found that SMPDL3B expression was upregulated from week 10 to 18 in the retinal tissues of db/db mice. Particularly, the high expression of SMPDL3B was mainly observed in retinal vascular endothelium of DR mice. To interfere retinal SMPDL3B expression, adeno-associated viruses 2 (AAV-2) containing SMPDL3B specific shRNA (1233-1253 bp) were injected into the vitreous cavity of db/db mice. SMPDL3B silencing exacerbated the spontaneous DR by further activating the NF-κB/NLRP3 pro-inflammatory pathway. In vitro, human retinal microvascular endothelial cells (HRVECs) were infected with SMPDL3B-shRNA lentiviruses and then stimulated with 30 mM glucose (HG) for 24 h. SMPDL3B-silenced HRVECs secreted more interleukin-1β and had enhanced nuclear p65 translocation. Notably, HG treatment induced the palmitoylation of SMPDL3B. Zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5) is a palmitoyltransferase that catalyzes the palmitoylation of its substrates, HG exposure increased the interaction between ZDHHC5 and SMPDL3B in HRVECs. 2-BP, a palmitoylation inhibitor, accelerated the protein degradation of SMPDL3B, whereas palmostatin B, a depalmitoylation inhibitor, decreased its turnover rate in HRVECs. Collectively, the present study suggests a compensatory increase of SMPDL3B in HG-treated HRVECs and the retinal tissues of DR mice, indicating that SMPDL3B may be a potential target for DR treatment.

2024-04-01·Translational Cancer Research

Contribution of sphingomyelin phosphodiesterase acid-like 3B to the proliferation, migration, and invasion of ovarian cancer cells

Article

作者: Jiang, Yatao ; Jiang, Yu ; Song, Baozhi ; Lin, Ying ; Liu, Jiahua

BackgroundCancer has the highest mortality rate among gynecological cancers and poses a serious threat to women's lives. However, the treatment options for ovarian cancer are still limited, and exploring effective targeted biomarkers is particularly important for predicting and treating ovarian cancer. Therefore, it is necessary to explore the molecular mechanisms of the occurrence and development of ovarian cancer.MethodsThis investigation encompassed the analysis of gene expression profiles, measurement of transcription levels of potential target genes in peripheral blood samples from ovarian cancer patients and characterization of the ovarian cancer-related secretory protein sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B). Through bioinformatics analysis, potential target genes were identified, and their association with overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients was assessed utilizing relevant databases. Subsequently, differences in target gene expression in ovarian cancer tissue samples were validated through protein blotting and quantitative real-time PCR (qRT-qPCR). Cell proliferation assays using the cell count kit-8 (CCK-8) method, as well as transwell chamber assay and pre coated matrix gel chamber assay were employed to elucidate the role of SMPDL3B in ovarian cancer cell migration and invasion.ResultsThis study revealed a substantial upregulation of SMPDL3B in the serum of ovarian cancer patients, correlating with an unfavorable prognosis. High SMPDL3B expression was linked not only to increased proliferation of ovarian cancer cells, but also enhanced migration and invasion. Remarkably, the knockdown the human alkaline ceramidase 2 (ACER2) gene in cancer cells with heightened SMPDL3B expression significantly inhibited cell proliferation, migration, and invasion induced by SMPDL3B activation (P<0.05), highlighting the functional interplay between ACER2 and SMPDL3B in ovarian cancer.ConclusionsIn summary, this study proposes SMPDL3B as a prognostic marker for ovarian cancer, with implications for potential therapeutic intervention targeting the ACER2-SMPDL3B axis.

2023-11-02·Fetal and Pediatric Pathology

The Importance of Sphingomyelin Phosphodiesterase Acid-Like 3b (SMPDL-3b) Levels in Kidney Biopsy Specimens of Children With Nephrotic Syndrome

Article

作者: Şenol, Hande ; Becerir, Tülay ; Yalçın, Nagihan ; Girişgen, İlknur ; Kaya, Muhammet ; Yüksel, Selcuk ; Gülten, Gülsün

OBJECTIVEIt remains unclear whether the low amount of SMPDL-3b required for rituximab binding is the cause of treatment resistance in patients with treatment-resistant nephrotic syndrome with advanced podocyte injury. Given the limited number of studies on the relationship between rituximab and SMPDL-3b, this study was conducted to assess whether SMPDL-3b levels in pretreatment renal biopsy specimens can be used to predict the clinical effectiveness of immunosuppressive drugs, especially rituximab, in children with nephrotic syndrome.METHODSKidney biopsy specimens from 44 patients diagnosed with idiopatic nephrotic syndrome were analyzed using immunohistochemical staining with an anti-SMPDL-3b antibody and real-time polymerase chain reaction (PCR) for SMPDL-3b mRNA expression.RESULTSWe showed that SMPDL-3b mRNA expression and anti-SMPDL-3b antibody staining did not differ significantly between the patient groups with different responses to immunosuppressive therapies.CONCLUSIONOur results suggest that SMPDL-3b may actually be an indicator of disease progression rather than a marker for predicting response to a particular immunosuppressive agent.

项与 SMPDL3B 相关的新闻（医药）

2023-05-29

·生物谷

Cancer Cell：何川/罗成等发现抑制YTHDF2可增强放疗的抗肿瘤疗效

目前，50-60%的癌症患者采用放射治疗（Radiation Therapy，RT），尽管技术和治疗方法不断改进，但很多患者由于耐药或转移而导致治疗失败。放射增敏治疗策略一般集中在抑制DNA修复或增加目前，50-60%的癌症患者采用放射治疗（Radiation Therapy，RT），尽管技术和治疗方法不断改进，但很多患者由于耐药或转移而导致治疗失败。放射增敏治疗策略一般集中在抑制DNA修复或增加DNA损伤上，其中免疫环境对治愈性至关重要。临床前数据表明，电离辐射（Ionizing Radiation，IR）单独或联合免疫检查点阻断具有免疫刺激作用。基于此，越来越多的临床试验启动免疫检查点阻断与IR联合疗法。然而，目前治疗效果有限，放疗联合免疫检查点疗法的协同作用机制及两者之间的相互关系仍需进一步探索。 N6-甲基腺苷（m6A）是真核生物中最常见的mRNA的修饰，主要调控mRNA的稳定性和翻译效率。m6A主要由RNA甲基转移酶（writer）—METTL3/METTL14、RNA去甲基化酶（eraser）—FTO和ALKBH5动态调控，随后由“阅读子”（reader）—YTHDF1/2/3和YTHDC1/2识别调节RNA代谢。研究表明，YTHDF2参与调控多种生物学过程，包括细胞周期进程，应激反应等，并与多种肿瘤生长有关。然而，YTHDF2在免疫细胞中的调控作用，尤其是在放疗和免疫治疗中的作用尚未被深入探讨。 2023年5月25日，芝加哥大学 Ralph Weichselbaum 教授、何川教授、Hua Laura Liang 教授与中国科学院上海药物研究所罗成研究员等在 Cancer Cell 期刊发表了题为：YTHDF2 inhibition potentiates radiotherapy anti-tumor efficacy 的研究论文。该研究发现，YTHDF2可作为放疗和放疗/免疫联合疗法的潜在靶点，提出了通过抑制YTHDF2来增强临床放射治疗效果的新策略。该研究发现，电离辐射（IR）在小鼠模型和人体内均可诱导免疫抑制性MDSC扩增和YTHDF2表达。IR介导放疗后，表达YTHDF2的MDSC群体增加，这与放疗后的转移进展有关。因此，研究人员猜想YTHDF2的增加是影响放疗效果的原因。于是，研究人员通过构建Ythdf2敲除小鼠模型，发现IR后，Ythdf2的缺失可改变MDSC分化，抑制MDSC向肿瘤转运，并减弱其抑制功能，增强了抗肿瘤免疫，从而增强了局部肿瘤IR的功效。进一步，研究人员发现，IR诱导的YTHDF2表达上调主要依赖于NF-κB/RELA信号通路。反过来，上调的YTHDF2通过直接结合并降解编码NF-κB信号负调控因子（Adrb2、Metrnl和Smpdl3b）的转录本，导致NF-κB活化，从而形成 IR-YTHDF2-NF-κB回路。这些都表明，可以通过抑制YTHDF2来提高抗肿瘤免疫和放疗效果，其有望成为临床放射治疗的新策略。为了进一步证明YTHDF2是潜在的改善放疗和RT/免疫联合疗法的靶点，研究人员通过靶向YTHDF2开展化学干预研究。基于建立的化合物高通量筛选方法，开展了小分子抑制剂的筛选并获得了YTHDF2的活性化合物DC-Y13。通过结构改造获得了化合物DC-Y13-27，其可以在体外直接结YTHDF2蛋白并抑制其与m6A-RNA的结合。此外，DC-Y13-27在小鼠上与敲除YTHDF2类似，不仅可有效提高的IR疗效，而且提高了IR与PD-L1抗体联合治疗的抗肿瘤效果。抑制YTHDF2克服了MDSC诱导的免疫抑制，不仅可以改善局部肿瘤治疗效果，还可以抑制肿瘤转移。