Evidence map›Paper›PMID 40361216›Full record

ArticleSkeletal muscle2025

GsMTx4-blocked PIEZO1 channel promotes myogenic differentiation and alleviates myofiber damage in Duchenne muscular dystrophy.

Wengang Wang, Mingyang Huang, Xiusheng Huang, Ke Ma, Ming Luo, Ningning Yang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Skeletal muscle, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

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3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

6 authors.

Wengang Wang *Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Mingyang Huang *Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Xiusheng Huang *Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Ke MaDepartment of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Ming LuoDepartment of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. luoming1027@whu.edu.cn.
Ningning YangDepartment of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. yangningningzzu@126.com.

Funding

The Central High-Level Hospital Clinical Research Funding 2022-PUMCH-D-004The Medical Science and Technology Project of Henan Province LHGJ20230198The National Natural Science Foundation of China 82202767
6 · The paper itself

Abstract

backgroundDuchenne muscular dystrophy (DMD) is a debilitating disease characterized by progressive muscle-wasting and a lack of effective therapy. Although the application of GsMTx4 has been shown to reduce muscle mass loss in dystrophic mice, the mechanism of action remains unclear.

methodsWe employed single-nucleus RNA sequencing data to scrutinize the expression of mechanosensitive channels in skeletal muscle. The upregulation of PIEZO1 and its precise localization were corroborated in DMD patients, mdx mice, and activated satellite cells. To delve into the role of the GsMTx4-blocked PIEZO1 channel in the myogenic program, we conducted comprehensive in vitro and in vivo studies encompassing the proliferation of satellite cells, differentiation of myoblasts, and calcium influx into myofibers. Utilizing both a PIEZO1 channel inhibitor, GsMTx4, and a PIEZO1 channel agonist, Yoda1, we explored the PIEZO1 channel's impact on satellite cell proliferation and myogenic differentiation. Additionally, we explored the protective effect of the PIEZO1 channel on myofiber calcium influx using mdx mouse models and isolated single myofibers.

resultsPIEZO1 was upregulated in the muscle of DMD patients and was predominantly expressed in satellite cells and upregulated during satellite cell proliferation. Treatment with GsMTx4 increased the cross-sectional areas of myofibers and reduced the proportion of centrally nucleated fibers in mdx mice. GsMTx4 inhibited satellite cell proliferation while promoting myogenic differentiation. During myogenic differentiation, the YAP nuclear-cytoplasmic ratio increased in cells treated with GsMTx4 and showed a significant correlation with the nuclear localization of MyoG. In myofibers, GsMTx4 significantly reduced the level of p-CaMKII/CaMKII in muscle and calcium load.

conclusionsPIEZO1 upregulation in DMD could potentially stem from an elevated proportion of proliferating satellite cells triggered by sarcolemma damage and muscle necrosis. The inhibition of the PIEZO1 channel by GsMTx4 plays a beneficial role in fostering myogenic differentiation and mitigating myofiber damage. The PIEZO1 channel emerges as a promising therapeutic target for addressing DMD.

Indexed as

Ion ChannelsMuscle DevelopmentMuscle Fibers, SkeletalMuscular Dystrophy, DuchenneSpider VenomsAnimalsCalciumCell DifferentiationCell ProliferationHumansIntercellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLMice, Inbred mdxMuscle, SkeletalCalciumIntercellular Signaling Peptides and ProteinsIon ChannelsMTx4 protein, Grammostola spatulataPIEZO1 protein, humanPiezo1 protein, mouseSpider VenomsDuchenne muscular dystrophyGsMTx4Myogenic differentiationPIEZO1Satellite cells

Identifiers

PMID40361216
PMCPMC12076844

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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.