Activation of Piezo1 promotes osteogenic differentiation of aortic valve interstitial cell through YAP-dependent glutaminolysis

Zhong, Guoheng; Su, Sheng; Li, Juncong; Zhao, Hengli; Hu, Dongtu; Chen, Jun; Li, Shichao; Lin, Yingwen; Wen, Li; Lin, Xiaochang; Xian, Gaopeng; Xu, Dingli; Zeng, Qingchun

doi:10.1126/sciadv.adg0478

Cited by 27 publications

(8 citation statements)

References 67 publications

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“…Piezo1 mediates distinct Ca 2+ signaling pathways to regulate cellular activities [ 9 ]. Yes-associated protein (Yap) has been shown to be an important downstream mechanotransduction effector of Piezo1 [ 43 ]. A recent study showed that the double-knockout of Yap/Taz in smooth muscle significantly downregulated the expression of colonic motility-related genes (such as Tpm1, Actg2, Acta2) and impaired colonic contractility, causing colonic pseudo-obstruction and lethality [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Slowed Intestinal Transit Induced by Less Mucus in Intestinal Goblet Cell Piezo1-Deficient Mice through Impaired Epithelial Homeostasis

Fang,

Liu,

Xiong

et al. 2023

IJMS

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Mucus secreted by goblet cells (GCs) may play an important role in intestinal transit function. Our previous study found that Piezo1 protein is essential for GC function; however, the effect of GC Piezo1 on intestinal transit function is unclear. Our study aimed to investigate the effect of Piezo1 in GCs on intestinal transit and the potential mechanism. We compared intestinal mucus, fecal form, intestinal transit time, intestinal epithelial cell composition, and stem cell function in WT and GC-specific Piezo1-deficient (Piezo1ΔGC) mice. Our results revealed a correlation between mucus and intestinal transit: the less mucus there was, the slower the intestinal transit. Piezo1 deficiency in GCs led to decreased mucus synthesis and also disrupted the ecological niche of colon stem cells (CSCs). Through organoid culture, we found that the capacity of proliferation and differentiation in Piezo1ΔGC mouse CSCs was significantly decreased, which also led to a reduced source of GCs. Further studies found that the reduced Wnt and Notch signals in colon crypts might be the potential mechanism. These results indicated the importance of GC Piezo1 in intestinal transit function, which acts by maintaining the homeostasis of intestinal epithelial cells and mucus.

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Section: Discussionmentioning

confidence: 99%

Slowed Intestinal Transit Induced by Less Mucus in Intestinal Goblet Cell Piezo1-Deficient Mice through Impaired Epithelial Homeostasis

Fang,

Liu,

Xiong

et al. 2023

IJMS

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“…no. bes5001, Guangzhou Bersinbio Co., Ltd.) was used with slight modifications to the manufacturer's protocol ( 18 ). Cells were crosslinked using 1% formaldehyde and the reaction was terminated by adding glycine to a final concentration of 0.125 M. The E2F1 antibodies (1:100) were used to immunoprecipitate DNA from sonicated cell lysates, with IgG (BD Biosciences) as the negative control.…”

Section: Methodsmentioning

confidence: 99%

Long non‑coding RNA DANCR aggravates breast cancer through the miR‑34c/E2F1 feedback loop

Yan,

Teng,

et al. 2024

Mol Med Rep

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Emerging scientific evidence has suggested that the long non-coding (lnc)RNA differentiation antagonizing non-protein coding RNA ( DANCR ) serves a significant role in human tumorigenesis and cancer progression; however, the precise mechanism of its function in breast cancer remains to be fully understood. Therefore, the objective of the present study was to manipulate DANCR expression in MCF7 and MDA-MB-231 cells using lentiviral vectors to knock down or overexpress DANCR . This manipulation, alongside the analysis of bioinformatics data, was performed to investigate the potential mechanism underlying the role of DANCR in cancer. The mRNA and/or protein expression levels of DANCR, miR-34c-5p and E2F transcription factor 1 ( E2F1 ) were assessed using reverse transcription-quantitative PCR and western blotting, respectively. The interactions between these molecules were validated using chromatin immunoprecipitation and dual-luciferase reporter assays. Additionally, fluorescence in situ hybridization was used to confirm the subcellular localization of DANCR . Cell proliferation, migration and invasion were determined using 5-ethynyl-2′-deoxyuridine, wound healing and Transwell assays, respectively. The results of the present study demonstrated that DANCR had a regulatory role as a competing endogenous RNA and upregulated the expression of E2F1 by sequestering miR-34c-5p in breast cancer cells. Furthermore, E2F1 promoted DANCR transcription by binding to its promoter in breast cancer cells. Notably, the DANCR / miR-34c-5p / E2F1 feedback loop enhanced cell proliferation, migration and invasion in breast cancer cells. Thus, these findings suggested that targeting DANCR may potentially provide a promising future therapeutic strategy for breast cancer treatment.

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“…For example, Zhong et al verified that Piezo1 activated by mechanical stress was able to regulate glutaminase 1 (GLS1)-mediated glutaminolysis and advance osteogenic differentiation of valve interstitial cells, whereas inhibition or knockdown of Piezo1 and GLS1 respectively diminished these effects. Mechanistically, activation of Piezo1 promoted calciumdependent YAP activation, thereby regulating GLS1-mediated glutaminolysis and enhancing osteogenic differentiation through histone acetylation of runt-related transcription factor 2 promoter [38]. Another study by Li suggested that mechanical stress accelerated the osteogenesis and angiogenesis of tissueengineered laminae through the F-actin/YAP-1/β-Catenin signaling axis.…”

Section: Hippo/yap and Regenerationmentioning

confidence: 99%

The roles of Hippo/YAP signaling pathway in physical therapy

Pan,

Hao,

Deng

et al. 2024

Cell Death Discov.

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Cellular behavior is regulated by mechanical signals within the cellular microenvironment. Additionally, changes of temperature, blood flow, and muscle contraction also affect cellular state and the development of diseases. In clinical practice, physical therapy techniques such as ultrasound, vibration, exercise, cold therapy, and hyperthermia are commonly employed to alleviate pain and treat diseases. However, the molecular mechanism about how these physiotherapy methods stimulate local tissues and control gene expression remains unknow. Fortunately, the discovery of YAP filled this gap, which has been reported has the ability to sense and convert a wide variety of mechanical signals into cell-specific programs for transcription, thereby offering a fresh perspective on the mechanisms by which physiotherapy treat different diseases. This review examines the involvement of Hippo/YAP signaling pathway in various diseases and its role in different physical therapy approaches on diseases. Furthermore, we explore the potential therapeutic implications of the Hippo/YAP signaling pathway and address the limitations and controversies surrounding its application in physiotherapy.

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Activation of Piezo1 promotes osteogenic differentiation of aortic valve interstitial cell through YAP-dependent glutaminolysis

Cited by 27 publications

References 67 publications

Slowed Intestinal Transit Induced by Less Mucus in Intestinal Goblet Cell Piezo1-Deficient Mice through Impaired Epithelial Homeostasis

Slowed Intestinal Transit Induced by Less Mucus in Intestinal Goblet Cell Piezo1-Deficient Mice through Impaired Epithelial Homeostasis

Long non‑coding RNA DANCR aggravates breast cancer through the miR‑34c/E2F1 feedback loop

The roles of Hippo/YAP signaling pathway in physical therapy

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