Evidence map›Paper›PMID 38573820›Full record

ArticleeLife2024

Activating SRC/MAPK signaling via 5-HT1A receptor contributes to the effect of vilazodone on improving thrombocytopenia.

Ling Zhou, Chengyang Ni, Ruixue Liao, Xiaoqin Tang, Taian Yi, Mei Ran, Miao Huang, Rui Liao, Xiaogang Zhou, Dalian Qin and 7 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 3 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 2 institutions in 1 country.

Ling Zhou *Sichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, LuZhou, China.ORCID https://orcid.org/0000-0001-8620-5557
Chengyang Ni *Sichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, LuZhou, China.
Ruixue Liao *Sichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, LuZhou, China.
Xiaoqin TangSichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, LuZhou, China.
Taian YiSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Mei RanSichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, LuZhou, China.
Miao HuangSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Rui LiaoSichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, LuZhou, China.
Xiaogang ZhouSichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, LuZhou, China.
Dalian QinSichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, LuZhou, China.
Long WangSichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, LuZhou, China.
Feihong HuangSichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, LuZhou, China.
Xiang XieSchool of Basic Medical Sciences, Public Center of Experimental Technology, Model Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, China.
Ying WanSchool of Basic Medical Sciences, Southwest Medical University, Luzhou, China.
Jiesi LuoSchool of Basic Medical Sciences, Southwest Medical University, Luzhou, China.
Yiwei WangSchool of Basic Medical Sciences, Southwest Medical University, Luzhou, China.
Jianming WuSichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, LuZhou, China.ORCID https://orcid.org/0000-0002-6136-7469
Southwest Medical University · CNChengdu University of Traditional Chinese Medicine · CN

Funding

National Natural Science Foundation of China 82004073National Natural Science Foundation of China 82074129National Natural Science Foundation of China 82374073Natural Science Foundation of Sichuan Province 2022JDJQ0061Natural Science Foundation of Sichuan Province 2022YFS0607Natural Science Foundation of Sichuan Province 2022YFS0614Natural Science Foundation of Sichuan Province 2022ZYD0087Natural Science Foundation of Sichuan Province 22ZYZYTS0191Science and Technology Planning Project of Luzhou City 2020LZXNYDP01Science and Technology Planning Project of Luzhou City 2020LZXNYDZ03
6 · The paper itself

Abstract

Thrombocytopenia caused by long-term radiotherapy and chemotherapy exists in cancer treatment. Previous research demonstrates that 5-Hydroxtrayptamine (5-HT) and its receptors induce the formation of megakaryocytes (MKs) and platelets. However, the relationships between 5-HT1A receptor (5-HTR1A) and MKs is unclear so far. We screened and investigated the mechanism of vilazodone as a 5-HTR1A partial agonist in promoting MK differentiation and evaluated its therapeutic effect in thrombocytopenia. We employed a drug screening model based on machine learning (ML) to screen the megakaryocytopoiesis activity of Vilazodone (VLZ). The effects of VLZ on megakaryocytopoiesis were verified in HEL and Meg-01 cells. Tg (itga2b: eGFP) zebrafish was performed to analyze the alterations in thrombopoiesis. Moreover, we established a thrombocytopenia mice model to investigate how VLZ administration accelerates platelet recovery and function. We carried out network pharmacology, Western blot, and immunofluorescence to demonstrate the potential targets and pathway of VLZ. VLZ has been predicted to have a potential biological action. Meanwhile, VLZ administration promotes MK differentiation and thrombopoiesis in cells and zebrafish models. Progressive experiments showed that VLZ has a potential therapeutic effect on radiation-induced thrombocytopenia in vivo. The network pharmacology and associated mechanism study indicated that SRC and MAPK signaling are both involved in the processes of megakaryopoiesis facilitated by VLZ. Furthermore, the expression of 5-HTR1A during megakaryocyte differentiation is closely related to the activation of SRC and MAPK. Our findings demonstrated that the expression of 5-HTR1A on MK, VLZ could bind to the 5-HTR1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production, which provides new insights into the alternative therapeutic options for thrombocytopenia.

Indexed as

ThrombocytopeniaVilazodone HydrochlorideAnimalsBlood PlateletsMegakaryocytesMiceReceptor, Serotonin, 5-HT1AThrombopoiesisZebrafishReceptor, Serotonin, 5-HT1AVilazodone Hydrochloride5-HT1A receptormedicinemegakaryocytemousethrombocytopeniavilazodone

Identifiers

PMID38573820
PMCPMC10994662
OpenAlexW4391812729

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.