Mechanical stretch promotes hypertrophic scar formation through mechanically activated cation channel Piezo1

He, Jiahao; Fang, Bin; Shan, Shengzhou; Xie, Yun; Wang, Chuandong; Zhang, Yifan; Zhang, Xiaoling; Li, Qingfeng

doi:10.1038/s41419-021-03481-6

Cited by 82 publications

(87 citation statements)

References 69 publications

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“…CXCL1, as a neutrophil chemoattractant, induces sinusoidal thromboses, portal hypertension and fibrogenesis. In a recent study, increased Piezo1 expression was found in hypertrophic scars and was shown to participate in scar formation ( He et al, 2021 ).…”

Section: Cellular Mechanotransduction In Fibrosismentioning

confidence: 99%

Focusing on Mechanoregulation Axis in Fibrosis: Sensing, Transduction and Effecting

Wen

Gao

et al. 2022

Front. Mol. Biosci.

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Fibrosis, a pathologic process featured by the excessive deposition of connective tissue components, can affect virtually every organ and has no satisfactory therapy yet. Fibrotic diseases are often associated with organ dysfunction which leads to high morbidity and mortality. Biomechanical stmuli and the corresponding cellular response havebeen identified in fibrogenesis, as the fibrotic remodeling could be seen as the incapacity to reestablish mechanical homeostasis: along with extracellular matrix accumulating, the physical property became more “stiff” and could in turn induce fibrosis. In this review, we provide a comprehensive overview of mechanoregulation in fibrosis, from initialing cellular mechanosensing to intracellular mechanotransduction and processing, and ends up in mechanoeffecting. Our contents are not limited to the cellular mechanism, but further expand to the disorders involved and current clinical trials, providing an insight into the disease and hopefully inspiring new approaches for the treatment of tissue fibrosis.

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Section: Cellular Mechanotransduction In Fibrosismentioning

confidence: 99%

Focusing on Mechanoregulation Axis in Fibrosis: Sensing, Transduction and Effecting

Wen

Gao

et al. 2022

Front. Mol. Biosci.

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“…This elevated Ca 2+ entry upon PIEZO1 activation is correlated with an increased Il-6 gene expression, p38 phosphorylation and TNC mRNA and protein expression, consistent with previous findings from our group [ 13 , 15 , 35 ]. Furthermore, PIEZO1-mediated Ca 2+ influx is involved in inflammatory pathways including the IL-6 receptor family and Ca 2+ -sensitive MAPK family such as p38 in various systems (e.g., renal fibrosis models, liver carcinoma cell lines or human dermal fibroblasts) [ 13 , 14 , 17 , 64 , 65 , 66 , 67 ]. IL-6 has been characterised as a key regulator of inflammation [ 68 , 69 , 70 ] and described as cardioprotective in the initial inflammatory response to cardiac pathology [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

Global PIEZO1 Gain-of-Function Mutation Causes Cardiac Hypertrophy and Fibrosis in Mice

Bartoli

Evans

Blythe

et al. 2022

Cells

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PIEZO1 is a subunit of mechanically-activated, nonselective cation channels. Gain-of-function PIEZO1 mutations are associated with dehydrated hereditary stomatocytosis (DHS), a type of anaemia, due to abnormal red blood cell function. Here, we hypothesised additional effects on the heart. Consistent with this hypothesis, mice engineered to contain the M2241R mutation in PIEZO1 to mimic a DHS mutation had increased cardiac mass and interventricular septum thickness at 8–12 weeks of age, without altered cardiac contractility. Myocyte size was greater and there was increased expression of genes associated with cardiac hypertrophy (Anp, Acta1 and β-MHC). There was also cardiac fibrosis, increased expression of Col3a1 (a gene associated with fibrosis) and increased responses of isolated cardiac fibroblasts to PIEZO1 agonism. The data suggest detrimental effects of excess PIEZO1 activity on the heart, mediated in part by amplified PIEZO1 function in cardiac fibroblasts.

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“…The Piezo1 channel has been identified as a new mechanically activated cation channel (MAC) reportedly capable of modulating force-mediated cellular biological behavior. In hypertrophic scars, cycling mechanical stretching increased Piezo1 expression and promoted proliferation, migration, and differentiation of human skin fibroblasts and activated Piezo1-mediated influx of calcium ( He et al, 2021 ). Yan et al (2021 ) demonstrated phosphoproteome and biological evidence of abnormal calcium homeostasis and induction of abnormal platelet aggregation in keloid fibroblasts.…”

Section: Biomechanical Factors and Mechanotransduction Pathways In Ke...mentioning

confidence: 99%

Biomechanical Regulatory Factors and Therapeutic Targets in Keloid Fibrosis

et al. 2022

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Keloids are fibroproliferative skin disorder caused by abnormal healing of injured or irritated skin and are characterized by excessive extracellular matrix (ECM) synthesis and deposition, which results in excessive collagen disorders and calcinosis, increasing the remodeling and stiffness of keloid matrix. The pathogenesis of keloid is very complex, and may include changes in cell function, genetics, inflammation, and other factors. In this review, we aim to discuss the role of biomechanical factors in keloid formation. Mechanical stimulation can lead to excessive proliferation of wound fibroblasts, deposition of ECM, secretion of more pro-fibrosis factors, and continuous increase of keloid matrix stiffness. Matrix mechanics resulting from increased matrix stiffness further activates the fibrotic phenotype of keloid fibroblasts, thus forming a loop that continuously invades the surrounding normal tissue. In this process, mechanical force is one of the initial factors of keloid formation, and matrix mechanics leads to further keloid development. Next, we summarized the mechanotransduction pathways involved in the formation of keloids, such as TGF-β/Smad signaling pathway, integrin signaling pathway, YAP/TAZ signaling pathway, and calcium ion pathway. Finally, some potential biomechanics-based therapeutic concepts and strategies are described in detail. Taken together, these findings underscore the importance of biomechanical factors in the formation and progression of keloids and highlight their regulatory value. These findings may help facilitate the development of pharmacological interventions that can ultimately prevent and reduce keloid formation and progression.

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Mechanical stretch promotes hypertrophic scar formation through mechanically activated cation channel Piezo1

Cited by 82 publications

References 69 publications

Focusing on Mechanoregulation Axis in Fibrosis: Sensing, Transduction and Effecting

Focusing on Mechanoregulation Axis in Fibrosis: Sensing, Transduction and Effecting

Global PIEZO1 Gain-of-Function Mutation Causes Cardiac Hypertrophy and Fibrosis in Mice

Biomechanical Regulatory Factors and Therapeutic Targets in Keloid Fibrosis

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