更新于：2024-11-01

GDF10

更新于：2024-11-01

基本信息

别名

BIP、BMP-3b、BMP3B

+ [6]

简介

Growth factor involved in osteogenesis and adipogenesis. Plays an inhibitory role in the process of osteoblast differentiation via SMAD2/3 pathway. Plays an inhibitory role in the process of adipogenesis.

关联

项与 GDF10 相关的药物

CN118421779

专利挖掘

靶点

GDF10

作用机制-

在研机构

复旦大学附属中山医院

原研机构

复旦大学附属中山医院

在研适应症

肝病

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 GDF10 相关的临床结果

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100 项与 GDF10 相关的转化医学

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0 项与 GDF10 相关的专利（医药）

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117

项与 GDF10 相关的文献（医药）

2024-11-01·Journal of Biological Chemistry

GDF10 is a negative regulator of vascular calcification

Article

作者: MacDonald, Melissa E ; Krepinsky, Joan C. ; Byun, Jae Hyun ; Igdoura, Suleiman A ; Krepinsky, Joan C ; Holden, Rachel M ; Roubtsova, Anna ; Austin, Richard C ; MacDonald, Melissa E. ; Seidah, Nabil G ; Igdoura, Suleiman A. ; Gyulay, Gabriel ; Seidah, Nabil G. ; Austin, Richard C. ; Holden, Rachel M. ; Platko, Khrystyna ; Lynn, Edward G. ; Lebeau, Paul F. ; Lynn, Edward G ; Lebeau, Paul F

Cardiovascular mortality is particularly high and increasing in patients with chronic kidney disease, with vascular calcification (VC) as a major pathophysiologic feature. VC is a highly regulated biological process similar to bone formation involving osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). We have previously demonstrated that loss of T-cell death-associated gene 51 (TDAG51) expression leads to an attenuation of medial VC. We now show a significant induction of circulating levels of growth differentiation factor 10 (GDF10) in TDAG51^-/- mice, which was of interest due to its established role as an inhibitor of osteoblast differentiation. The objective of this study was to examine the role of GDF10 in the osteogenic transdifferentiation of VSMCs. Using primary mouse and human VSMCs, as well as ex vivo aortic ring cultures, we demonstrated that treatment with recombinant human (rh) GDF10 mitigated phosphate-mediated hydroxyapatite (HA) mineral deposition. Furthermore, ex vivo aortic rings from GDF10^-/- mice exhibited increased HA deposition compared to C57BL/6J controls. To explain our observations, we identified that rhGDF10 treatment reduced protein expression of runt-related transcription factor 2, a key driver of osteogenic transdifferentiation of VSMCs and VC. In support of these findings, in vivo treatment with rhGDF10 attenuated VD₃-induced VC. Furthermore, we demonstrated an increase in circulating GDF10 in patients with chronic kidney disease with clinically defined severe VC, as assessed by coronary artery calcium score. Thus, our studies identify GDF10 as a novel inhibitor of mineral deposition and as such, may represent a potential novel biomarker and therapeutic target for the detection and management of VC.

2024-05-01·Chemosphere

Multilevel assessment of carbamazepine effects: An integrative approach using zebrafish early-life stages

Article

作者: Camargo, Níchollas Serafim ; Andrade, Thayres Sousa ; Pic-Taylor, Aline ; Grisolia, Cesar Koppe ; Silva, Muriel Lopes da ; Sousa-Moura, Diego ; Domingues, Inês ; Oliveira, Rhaul de ; Lisboa, Carolina Almeida ; Villacis, Rolando André Rios

Carbamazepine (CBZ) is the most commonly used drug in epilepsy treatment, and its metabolites are commonly detected among persistent pharmaceuticals in the aquatic environment. This study aimed to investigate CBZ effects on early-life-stage zebrafish (Danio rerio) (from 2 to 168 hpf) by employing of an integrative approach linking endpoints from molecular to individual level: (i) development; (ii) locomotor activity; (iii) biochemical markers (lactate dehydrogenase, glutathione-S-transferase, acetylcholinesterase and catalase) and (iv) transcriptome analysis using microarray. A 168 h - LC₅₀ of 73.4 mg L^-1 and a 72 h - EC₅₀ of 66.8 mg L^-1 for hatching were calculated while developmental effects (oedemas and tail deformities) were observed at CBZ concentrations above 37.3 mg L^-1. At the biochemical level, AChE activity proved to be the most sensitive parameter, as evidenced by its decrease across all concentrations tested (∼25% maximum reduction, LOEC (lowest observed effect concentration) < 0.6 μg L^-1). Locomotor behaviour seemed to be depressed by CBZ although this effect was only evident at the highest concentration tested (50 mg L^-1). Molecular analysis revealed a dose-dependent effect of CBZ on gene expression. Although only 25 genes were deregulated in organisms exposed to CBZ when compared to controls, both 0.6 and 2812 μg L^-1 treatments impaired gene expression related to development (e.g. crygmxl1, org, klf2a, otos, stx16 and tob2) and the nervous system (e.g. Rtn3, Gdf10, Rtn3), while activated genes were associated with behavioural response (e.g. prlbr and taar). Altogether, our results indicate that environmentally relevant CBZ concentrations might affect biochemical and genetic traits of fish. Thus, the environmental risk of CBZ cannot be neglected, especially in a realistic scenario of constant input of domestic effluents into aquatic systems.

2024-04-01·Current Medical Science

Diagnostic Value of GDF10 for the Tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma

Article

作者: Chen, Jia-Ping ; Mei, Pei-Yuan ; Xiao, Han ; Wang, Xiao-Jun ; Zhao, Rong ; Lin, Wei ; Wang, Yang-Wei ; Meng, Yun-Chong ; Qiao, Xin-Wei ; Meng, Wang-Yang ; Liao, Yong-de

OBJECTIVELung squamous cell carcinoma (LUSC) is associated with a low survival rate. Evidence suggests that bone morphogenetic proteins (BMPs) and their receptors (BMPRs) play crucial roles in tumorigenesis and progression. However, a comprehensive analysis of their role in LUSC is lacking. Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.METHODSThe "R/Limma" package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC, using data from TCGA, GTEx, and GEO databases. Concurrently, the "survminer" packages were employed to investigate their prognostic value and correlation with clinical features in LUSC. The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis (WGCNA). LASSO analysis was conducted to construct a prognostic risk model for LUSC. Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC. Furthermore, based on the tumor immune estimation resource database and tumor-immune system interaction database, the role of the core gene in the tumor microenvironment of LUSC was explored.RESULTSGDF10 had a significant correlation only with the pathological T stage of LUSC, and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC. A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes (HRASLS, HIST1H2BH, FLRT3, CHEK2, and ALPL) for LUSC. GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.CONCLUSIONGDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.