THSD1

Last update 23 Jan 2025

Basic Info

Synonyms

thrombospondin type 1 domain containing 1, Thrombospondin type-1 domain-containing protein 1, THSD1

+ [2]

Introduction

Is a positive regulator of nascent focal adhesion assembly, involved in the modulation of endothelial cell attachment to the extracellular matrix.

100 Clinical Results associated with THSD1

100 Translational Medicine associated with THSD1

0 Patents (Medical) associated with THSD1

1,388

Literatures (Medical) associated with THSD1

02 Jan 2025·Cancer Research

HIF1α Counteracts TGFβ1-Driven TSP1 Expression in Endothelial Cells to Stimulate Angiogenesis in the Hypoxic Tumor Microenvironment

Article

Author: Zhuang, Shi-Mei ; Fang, Jian-Hong ; Luo, Yu-Wei ; Chen, Jie-Ying ; Fang, Yang ; Li, Hui ; Zeng, Hui-Xian ; Zheng, Li-Min ; Wu, Meng-Zhi ; Ji, Yu-Chen

AbstractEmerging evidence suggests that TGFβ1 can inhibit angiogenesis, contradicting the coexistence of active angiogenesis and high abundance of TGFβ1 in the tumor microenvironment. Here, we investigated how tumors overcome the antiangiogenic effect of TGFβ1. TGFβ1 treatment suppressed physiologic angiogenesis in chick chorioallantoic membrane and zebrafish models but did not affect angiogenesis in mouse hepatoma xenografts. The suppressive effect of TGFβ1 on angiogenesis was recovered in mouse xenografts by a hypoxia-inducible factor 1α (HIF1α) inhibitor. In contrast, a HIF1α stabilizer abrogated angiogenesis in zebrafish, indicating that hypoxia may attenuate the antiangiogenic role of TGFβ1. Under normoxic conditions, TGFβ1 inhibited angiogenesis by upregulating antiangiogenic factor thrombospondin 1 (TSP1) in endothelial cells (EC) via TGFβ type I receptor (TGFβR1)–SMAD2/3 signaling. In a hypoxic microenvironment, HIF1α induced miR145 expression; miR145 abolished the inhibitory effect of TGFβ1 on angiogenesis by binding and repressing SMAD2/3 expression and subsequently reducing TSP1 levels in ECs. Primary ECs isolated from human hepatocellular carcinoma displayed increased miR145 and decreased SMAD3 and TSP1 compared with ECs from adjacent nontumor livers. The reduced SMAD3 or TSP1 in ECs was associated with increased angiogenesis in hepatocellular carcinoma tissues. Collectively, this study identified that TGFβ1–TGFβR1–SMAD2/3–TSP1 signaling in ECs inhibits angiogenesis. This inhibition can be circumvented by a hypoxia–HIF1α–miR145 axis, elucidating a mechanism by which hypoxia promotes angiogenesis.Significance: Suppression of angiogenesis by TGFβ1 is mediated by TSP1 upregulation in endothelial cells and abrogated by HIF1α–miR145 activity in the hypoxic tumor microenvironment, providing potential targets to remodel the tumor vasculature.

01 Jan 2025·Experimental Eye Research

Topical application of 666-15, a potent inhibitor of CREB, alleviates alkali-induced corneal neovascularization

Article

Author: Huang, Weifeng ; Su, Wenru ; Li, Zuohong ; Huang, Zhaohao ; Chen, Jianping ; Wang, Kerui ; Liang, Xuanwei

Corneal neovascularization (CNV) is a dynamically regulated process that arises due to a disruption in the equilibrium between pro-angiogenic and anti-angiogenic factors. Various cytokines are released by vascular endothelial cells and macrophages in damaged cornea, ultimately inducing CNV. The cAMP-response element-binding protein (CREB), a nuclear transcription factor, potentially impacts tumor angiogenesis by modulating the secretion of angiogenic proteins. This study aimed to assess the impact of 666-15, a potent inhibitor of CREB, on angiogenesis using human microvascular retinal endothelial cells (HMRECs), RAW 264.7 macrophage cell line and alkali-induce CNV mouse model. In vivo, the topical application of 666-15 (0.05 mg/mL) to the alkali-burn corneas led to 45% reduction in CNV. Additionally, in vitro treatment with 666-15 is effective in suppressing the migration, proliferation, and tube formation by HMRECs. Furthermore, treatment with 666-15 resulted in a down-regulation of pro-angiogenic cytokines expression, including VEGF-A, TGF-β1, b-FGF, and MMP-2 but simultaneously increasing anti-angiogenic cytokines expression, such as ADAMTS-1, Thrombospondin-1 (Tsp-1) and Tsp-2, both in alkali-burn corneas and HMRECs. And 666-15 inhibited the recruitment and the cytokines expression (VEGF-A, MMP-2, IL-1β, TNF-α, MCP-1 and MIP-1) of macrophage. Our findings revealed that 666-15 may suppress the function of endothelial cells and angiogenesis by restoring the homeostasis of pro-angiogenic stimuli, suggesting its potential as a therapeutic agent in the treatment of CNV and other angiogenesis-driven diseases.

01 Jan 2025·Drug Discovery Today

Novel therapeutic targets for cardiorenal syndrome

Review

Author: Gaikwad, Anil Bhanudas ; Jadhav, Hemant R ; Trivedi, Mansi Vinodkumar

Cardiorenal syndrome (CRS) is an interdependent dysfunction of the heart and kidneys, where failure in one organ precipitates failure in the other. The pathophysiology involves sustained renin-angiotensin-aldosterone-system (RAAS) activation, mitochondrial dysfunction, inflammation, fibrosis, oxidative stress and tissue remodeling, culminating in organ dysfunction. Existing therapies targeting the RAAS, diuretics and other agents have limitations, including diuretic resistance and compensatory sodium reabsorption. Therefore, there is a pressing need for novel druggable targets involved in CRS pathogenesis. This review addresses the challenges of existing treatments and emphasizes the importance of discovering new therapeutic targets. It highlights emerging targets such as Klotho, sex-determining region Y box 9 (SOX9), receptor-interacting protein kinase 3 (RIPK3), β-amino-isobutyric acid (BAIBA), thrombospondin-1 (TSP-1), among others, with their potential roles in CRS.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

THSD1

Basic Info

Related

Analysis