Isolation and Properties of a Thrombin-sensitive Protein of Human Platelets

Baenziger, Nancy Lewis; Brodie, G. N.; Majerus, Philip W.

doi:10.1016/s0021-9258(19)45271-x

Cited by 277 publications

(47 citation statements)

References 42 publications

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“…These pathogenic pathways and related substances can serve as new potential targets in CU. TGF-β Pathway Thrombospondin 1 Thrombospondin 1 (THBS1) encodes a common glycoprotein that was originally discovered as a thrombinsensitive protein [25]. It participates in many diseases such as antiphospholipid syndrome and diabetes [26,27].…”

Section: Biomarkers and Their Findings In Urticariamentioning

confidence: 99%

Advanced Biomarkers: Therapeutic and Diagnostic Targets in Urticaria

Zhang

et al. 2021

Int Arch Allergy Immunol

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Urticaria is a type of skin disease characterized by rapid onset of hives (superficial dermis edema, erythema, pruritus, or burning sensation). According to whether the natural course exceeds 6 weeks, urticaria can be divided into acute and chronic urticaria (CU). At present, the evaluation of CU activity mainly depends on the Urticaria Activity Score (UAS), but the evaluation indicators are relatively single, and we need more reliable experimental data for evaluation. We typically summarize advanced biomarkers and several related pathogenic pathways discovered in recent years on urticaria, including the cell adhesion/chemotaxis pathway, interleukin (IL)-6/Janus tyrosine kinase/STAT pathway, IL-17/IL-23 pathway, basophil- and mast cell-related pathway, coagulation/fibrinolysis-related pathways, single-nucleotide polymorphism, and some other pathways. This review aims to find appropriate biomarkers so that we can evaluate disease activity, discover novel therapeutic targets, and predict the patients’ response more accurately to therapeutic agents.

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Section: Biomarkers and Their Findings In Urticariamentioning

confidence: 99%

Advanced Biomarkers: Therapeutic and Diagnostic Targets in Urticaria

Zhang

et al. 2021

Int Arch Allergy Immunol

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“…However, upregulation of tissue TSP1 and/or circulating TSP1 can be found to be associated with various organ injuries and chronic clinical conditions [ 22 , 23 , 24 , 25 , 26 ]. TSP1 was first known to be stored and released from platelet α-granules upon activation [ 27 , 28 ]. Most of the commercially available TSP1 protein is extracted from human platelets.…”

Section: Representative Resultsmentioning

confidence: 99%

Efficient Ex Vivo Screening of Agents Targeting Thrombospondin1-Induced Vascular Dysfunction Using a Digital Multiwire Myograph System

Yao

Ganguly

Shin

et al. 2021

MPs

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Homeostasis of vascular tone is intricately and delicately maintained systemically and locally, by autonomic nerves and hormones in the blood and by intimal vasoactive substances, respectively. The balance can be acutely or chronically interrupted secondary to many alterations, especially under pathological conditions. Excessive matricellular glycoprotein thrombospondin 1 (TSP1) levels in circulation have been found to play an important role in ischemia-reperfusion injuries of different organs, by acutely suppressing vasorelaxation and chronically remodeling vascular bed. Our laboratory has been interested in identifying new drug moieties, which can selectively and effectively counteract TSP1-induced vascular dysfunction, in order to address associated clinical complications. Preliminary studies using computational docking and molecular models revealed potential drug candidates for further evaluation via vascular functional bioassay to prove the antagonism using an ex vivo vascular model. Herein, we described an efficient screening method for the identification of active drug candidates, by adapting a multiwire myograph system to perform a protocol with different treatments, in the presence of pathological levels of TSP1. We discussed the promising pharmacological evaluation results and suggested suitable modification for versatile applications. We also described the necessity of pre-determination of optimal resting tension to obtain the maximal response, if the experimental test model is different from those with determined optimal resting tension.

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“…TSP-1 is a matricellular protein with multiple properties, including the modulation of NO signals [ 13 ], immune cell recruitment and activation. TSP-1 was first discovered in platelets [ 14 , 15 ], endothelial cells [ 16 ], vascular smooth muscle cells [ 17 ] and in lymphoid or myeloid cells [ 18 , 19 ]. Its receptor, CD47, is expressed by T [ 20 ] and B cells [ 21 ], monocytes [ 22 ], platelets [ 23 ], erythrocyte precursors [ 24 ], vascular endothelial cells [ 25 ] and vascular smooth muscle cells [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Dual Role of Thrombospondin-1 in Flow-Induced Remodeling

Grenier

Caillon

Munier

et al. 2021

IJMS

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(1) Background: Chronic increases in blood flow, as in cardiovascular diseases, induce outward arterial remodeling. Thrombospondin-1 (TSP-1) is known to interact with matrix proteins and immune cell-surface receptors, but its contribution to flow-mediated remodeling in the microcirculation remains unknown. (2) Methods: Mesenteric arteries were ligated in vivo to generate high- (HF) and normal-flow (NF) arteries in wild-type (WT) and TSP-1-deleted mice (TSP-1−/−). After 7 days, arteries were isolated and studied ex vivo. (3) Results: Chronic increases in blood flow induced outward remodeling in WT mice (increasing diameter from 221 ± 10 to 280 ± 10 µm with 75 mmHg intraluminal pressure) without significant effect in TSP-1−/− (296 ± 18 to 303 ± 14 µm), neutropenic or adoptive bone marrow transfer mice. Four days after ligature, pro inflammatory gene expression levels (CD68, Cox2, Gp91phox, p47phox and p22phox) increased in WT HF arteries but not in TSP-1−/− mice. Perivascular neutrophil accumulation at day 4 was significantly lower in TSP-1−/− than in WT mice. (4) Conclusions: TSP-1 origin is important; indeed, circulating TSP-1 participates in vasodilation, whereas both circulating and tissue TSP-1 are involved in arterial wall thickness and diameter expansion.

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Isolation and Properties of a Thrombin-sensitive Protein of Human Platelets

Cited by 277 publications

References 42 publications

Advanced Biomarkers: Therapeutic and Diagnostic Targets in Urticaria

Advanced Biomarkers: Therapeutic and Diagnostic Targets in Urticaria

Efficient Ex Vivo Screening of Agents Targeting Thrombospondin1-Induced Vascular Dysfunction Using a Digital Multiwire Myograph System

Dual Role of Thrombospondin-1 in Flow-Induced Remodeling

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