更新于：2024-11-01

TGF-β1 x PDPN

更新于：2024-11-01

基本信息

关联

项与 TGF-β1 x PDPN 相关的药物

HB-001

靶点

PDPN x TGF-β1

作用机制

PDPN调节剂 [+1]

在研机构-

原研机构

华博生物医药技术（上海）有限公司 [+1]

在研适应症-

非在研适应症

肿瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 TGF-β1 x PDPN 相关的临床试验

JPRN-UMIN000036809 / Completed

Study of the safety and efficacy of brachytherapy (HB-001) by alpha-particle sources for refractory head & neck and breast cancer - Clinical Study of HB-001 brachytherapy in Japan

开始日期2019-05-25

申办/合作机构-

100 项与 TGF-β1 x PDPN 相关的临床结果

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100 项与 TGF-β1 x PDPN 相关的转化医学

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0 项与 TGF-β1 x PDPN 相关的专利（医药）

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项与 TGF-β1 x PDPN 相关的文献（医药）

2024-03-01·CNS Neuroscience & Therapeutics

Exosome‐transmitted podoplanin promotes tumor‐associated macrophage‐mediated immune tolerance in glioblastoma

Article

作者: Che, Jiajia ; Shi, Ying ; Huang, Hongxiang ; Shi, Jing ; Liu, Yuyang ; Wu, Mengwan ; Xu, Chuan

AbstractAimsGlioblastoma is the most frequent and aggressive primary brain tumor, characterized by rapid disease course and poor treatment responsiveness. The abundance of immunosuppressive macrophages in glioblastoma challenges the efficacy of novel immunotherapy.MethodsBulk RNA‐seq and single‐cell RNA‐seq of glioma patients from public databases were comprehensively analyzed to illustrate macrophage infiltration patterns and molecular characteristics of podoplanin (PDPN). Multiplexed fluorescence immunohistochemistry staining of PDPN, GFAP, CD68, and CD163 were performed in glioma tissue microarray. The impact of PDPN on macrophage immunosuppressive polarization was investigated using a co‐culture system. Bone marrow‐derived macrophages (BMDMs) and OT‐II T cells isolated from BALB/c and OT‐II mice respectively were co‐cultured to determine T‐cell adherence. Pathway alterations were probed through RNA sequencing and western blot analyses.ResultsOur findings demonstrated that PDPN is notably correlated with the expression of CD68 and CD163 in glioma tissues. Additionally, macrophages phagocytosing PDPN‐containing EVs (EVsPDPN) from GBM cells presented increased CD163 expression and augmented secretion of immunoregulatory cytokine (IL‐6, IL‐10, TNF‐α, and TGF‐β1). PDPN within EVs was also associated with enhanced phagocytic activity and reduced MHC II expression in macrophages, compromising CD4+ T‐cell activation.ConclusionsThis investigation underscores that EVsPDPN derived from glioblastoma cells contributes to M2 macrophage‐mediated immunosuppression and is a potential prognostic marker and therapeutic target in glioblastoma.

2022-05-01·Clinical Journal of the American Society of Nephrology

GWAS of Hematuria

Article

作者: Paterson, Andrew D. ; Sveinbjornsson, Gardar ; Gagliano Taliun, Sarah A. ; Barua, Moumita ; Stefansson, Kari ; Gudbjartsson, Daniel F. ; Sulem, Patrick

Background and objectivesGlomerular hematuria has varied causes but can have a genetic basis, including Alport syndrome and IgA nephropathy.Design, setting, participants, & measurementsWe used summary statistics to identify genetic variants associated with hematuria in White British UK Biobank participants. Individuals with glomerular hematuria were enriched by excluding participants with genitourinary conditions. A strongly associated locus on chromosome 2 (COL4A4-COL4A3) was identified. The region was reimputed using the Trans-Omics for Precision Medicine Program followed by sequential rounds of regional conditional analysis, conditioning on previous genetic signals. Similarly, we applied conditional analysis to identify independent variants in the MHC region on chromosome 6 using imputed HLA haplotypes.ResultsIn total, 16,866 hematuria cases and 391,420 controls were included. Cases had higher urinary albumin-creatinine compared with controls (women: 13.01 mg/g [8.05–21.33] versus 12.12 mg/g [7.61–19.29]; P<0.001; men: 8.85 mg/g [5.66–16.19] versus 7.52 mg/g [5.04–12.39]; P<0.001) and lower eGFR (women: 88±14 versus 90±13 ml/min per 1.72 m2; P<0.001; men: 87±15 versus 90±13 ml/min per 1.72 m2; P<0.001), supporting enrichment of glomerular hematuria. Variants at six loci (PDPN, COL4A4-COL4A3, HLA-B, SORL1, PLLP, and TGFB1) met genome-wide significance (P<5E-8). At chromosome 2, COL4A4 p.Ser969X (rs35138315; minor allele frequency=0.00035; P<7.95E-35; odds ratio, 87.3; 95% confidence interval, 47.9 to 159.0) had the most significant association, and two variants in the locus remained associated with hematuria after conditioning for this variant: COL4A3 p.Gly695Arg (rs200287952; minor allele frequency=0.00021; P<2.16E-7; odds ratio, 45.5; 95% confidence interval, 11.8 to 168.0) and a common COL4A4 intron 25 variant (not previously reported; rs58261427; minor allele frequency=0.214; P<2.00E-9; odds ratio, 1.09; 95% confidence interval, 1.06 to 1.12). Of the HLA haplotypes, HLA-B (*0801; minor allele frequency=0.14; P<4.41E-24; odds ratio, 0.84; 95% confidence interval, 0.82 to 0.88) displayed the most statistically significant association. For remaining loci, we identified three novel associations, which were replicated in the deCODE dataset for dipstick hematuria (nearest genes: PDPN, SORL1, and PLLP).ConclusionsOur study identifies six loci associated with hematuria, including independent variants in COL4A4-COL4A3 and HLA-B. Additionally, three novel loci are reported, including an association with an intronic variant in PDPN expressed in the podocyte.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_04_26_CJN13711021.mp3

2021-03-01·Lung Cancer2区 · 医学

Relationship between podoplanin-expressing cancer-associated fibroblasts and the immune microenvironment of early lung squamous cell carcinoma

2区 · 医学

Article

作者: Suzuki, Jun ; Tsuboi, Masahiro ; Kojima, Motohiro ; Miyoshi, Tomohiro ; Yamazaki, Shota ; Aokage, Keiju ; Ishii, Genichiro ; Sugano, Masato ; Hashimoto, Hiroko ; Kuwata, Takeshi ; Sakai, Takashi ; Fujii, Satoshi ; Neri, Shinya ; Nakamura, Hiroshi ; Su, Yinghan ; Ochiai, Atsushi ; Tane, Kenta

AIMCancer-associated fibroblasts (CAFs) expressing podoplanin (PDPN) harbor a fibrous tumor microenvironment that promotes cancer progression in lung adenocarcinoma. In this study, we investigated whether tumor-promoting PDPN⁺ CAFs contribute to the immunosuppressive microenvironment in lung squamous cell carcinoma (SqCC). M&M: The gene expression profiles of immunosuppressive cytokines were compared using The Cancer Genome Atlas (TCGA) microarray lung SqCC data (n = 484) between a PDPN-high group and a PDPN-low group. Further, using patient-derived CAFs from surgically resected lung SqCC, the PDPN⁺ fraction was sorted and gene and protein expressions were analyzed. Finally, immunohistochemical staining was conducted on 131 surgically resected lung SqCC; CD8⁺ and FOXP3⁺ tumor infiltrating lymphocytes (TILs), and CD204⁺ tumor-associated macrophages (TAMs) were evaluated in cases with PDPN⁺ and PDPN^- CAFs.RESULTSAnalysis of TCGA database revealed that the PDPN-high group exhibited significantly higher expression of interleukin (IL)-1A, IL-1B, IL-6, IL-10, monocyte chemoattractant protein-1 (CCL2), colony stimulating factor 1 (CSF1), fibroblast growth factor 2 (FGF2), galectin 1 (LGALS1), platelet derived growth factor subunit A (PDGFA), PDGFB, and transforming growth factor-β1 (TGFB1) than those in the PDPN-low group. Among them, it was found that TGFB1 expression was higher in patient-derived PDPN⁺ CAFs. Immunohistochemical analyses revealed that more CD204⁺ TAMs infiltrated the tumor tissues in cases with PDPN⁺ CAFs than in cases with PDPN^- CAFs (P <  0.03), while CD8⁺ and FOXP3⁺ TILs did not. Furthermore, in the same tumor, CD204⁺ TAMs infiltrated more in PDPN⁺ CAF-rich areas (P =  0.005).CONCLUSIONPDPN⁺ CAFs showed higher expression of TGFB1 and were associated with CD204⁺ TAM infiltration in stage-I lung SqCC, suggesting that PDPN⁺ CAFs were associated with the immunosuppressive tumor microenvironment.