Published: Oct. 30, 2024
Language: Английский
Published: Oct. 30, 2024
Language: Английский
Cell Reports, Journal Year: 2025, Volume and Issue: 44(3), P. 115400 - 115400
Published: March 1, 2025
Highlights•Piezo1 inhibition promotes colon stem cell proliferation•SCD1 is downstream of Piezo1 to affect stemness•Impaired stemness associated with fatty acid metabolism in crypts•GsMTX4 has a protective effect on injured colitis colonoidsSummaryPiezo1, which maintains the integrity and function intestinal epithelial barrier, essential for colonic homeostasis. However, whether how regulates fate remains unclear. Here, we show that proliferation. Mechanistically, stearoyl-CoA 9-desaturase 1 (SCD1) by acting Wnt-β-catenin pathway. For mice, altered after knockdown activation was accompanied reprogrammed (FA) crypts. Notably, found GsMTX4 protects mouse human organoids. Our results elucidated role regulating normal postinjury fates through SCD1-Wnt-β-catenin SCD1-mediated FA desaturation process. These provide fresh perspectives mechanical factors therapeutic strategies related diseases.Graphical abstract
Language: Английский
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1Critical Care, Journal Year: 2024, Volume and Issue: 28(1)
Published: May 15, 2024
Abstract Background Mechanical ventilation, a lifesaving intervention in critical care, can lead to damage the extracellular matrix (ECM), triggering inflammation and ventilator-induced lung injury (VILI), particularly conditions such as acute respiratory distress syndrome (ARDS). This review discusses detailed structure of ECM healthy ARDS-affected lungs under mechanical aiming bridge gap between experimental insights clinical practice by offering thorough understanding organization dynamics its alteration during ventilation. Main text Focusing on implications, we explore potential precise interventions targeting cellular signaling pathways mitigate damage, reduce inflammation, ultimately improve outcomes for critically ill patients. By analyzing range studies papers, particular attention is paid roles metalloproteinases (MMPs), integrins, other molecules VILI. synthesis not only sheds light structural changes induced stress but also underscores importance responses fibrosis, excessive activation MMPs. Conclusions emphasizes significance cues transduced integrins their impact behavior into complex interactions signaling. these mechanisms, healthcare professionals care anticipate consequences ventilation use targeted strategies prevent or minimize leading better patient management settings.
Language: Английский
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8Experimental Physiology, Journal Year: 2024, Volume and Issue: 109(9), P. 1545 - 1556
Published: July 9, 2024
Gut motility undergoes a switch from myogenic to neurogenic control in late embryonic development. Here, we report on the electrical events that underlie this transition enteric nervous system, using GCaMP6f reporter neural crest cell derivatives. We found spontaneous calcium activity is tetrodotoxin (TTX) resistant at stage E11.5, but not E18.5. Motility E18.5 was characterized by periodic, alternating high- and low-frequency contractions of circular smooth muscle; frequency modulation inhibited TTX. Calcium imaging neurogenic-motility stages E18.5-P3 showed Ca
Language: Английский
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4Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)
Published: March 12, 2025
Necrotizing enterocolitis (NEC) is a devastating inflammatory bowel necrosis of preterm infants with limited therapeutic approaches. Mounting evidence supports the role Piezo1, namely, widely distributed mechanosensor in intestinal epithelial cells (IECs), inflammation but its underlying mechanism development NEC remains unexplored. In this study, we demonstrated that Piezo1 expression was higher lower gestational age. C57BL/6J mice wherein deleted IECs (villin-specific knockout mice; Piezo1flox/floxVillinCre+) and Piezo1flox/flox littermates were subjected to induce NEC, regulated barrier function, restricted cytokines secretion, diminished response mouse models. elevated cytosolic Ca2+ levels activated Ca2+/calmodulin-dependent protein kinase II (CaMKII) promote CaMKII/NF-κB interaction NF-κB activation vitro. Finally, effects CaMKII inhibitor, KN93, evaluated both vitro vivo models, functions suppressed partially by KN93. characterise undefined which may be attributed differential calcium under pathophysiological conditions. Intestinal regulates secretion necrotizing enterocolitis.
Language: Английский
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0Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)
Published: April 22, 2025
Abstract Background Intestinal ischemia–reperfusion (I/R) injury, which occurs in the ileum and not only leads to intestinal tissue damage, but also may trigger systemic inflammatory responses, is a prevalent pathological condition that typically associated with acute ischemia, surgical procedures, or trauma. However, precise underlying pathogenic mechanisms have yet been fully uncovered. In this study, we explored specific roles by endothelial Piezo1 involved I/R injury. Methods We evaluated of using both vivo mouse injury vitro hypoxia-reoxygenation (H/R) models. The expression was assessed immunofluorescence RT-qPCR. experiments involving knockout activation agonist Yoda1 were conducted observe effects on angiogenesis Results found post-intestinal mice, markedly increased mainly abundant cells. Specific exhibited more severe phenotype characterized accelerating damage structure, increasing response, inhibiting angiogenesis. Yoda1-mediated significantly ameliorated Activation induced H/R promoted Human Umbilical Vein Endothelial Cells (HUVECs), inhibited GsMTx4. mediated linked an increase extracellular Ca 2+ influx, turn enhanced hypoxia-inducible factor 1 alpha (HIF-1α) signaling pathway. Conclusions Our findings indicate plays crucial role protecting against promoting cells, possibly through /HIF-1α/VEGF This suggests targeting channels could be therapeutic strategy for
Language: Английский
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0bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 7, 2024
Abstract Cell division is a major event in tissue homeostasis, enabling renewal and regeneration. Stem cells, particular, play an important role this thanks to their ability perform symmetric or asymmetric cell divisions. To study division, the human colon epithelium represents model of choice due its rapid therefore high proliferative potential. Currently, studying live mechanical interactions between matrix vivo challenging lack suitable methods. 3D organoids seeded Matrigel® are good models for purpose as, from isolated stem they recapitulate architecture organization properties. This culture set-up also allows displacements around organoid. Here, we studied impact within colonic on extracellular matrix. We performed validated original experimental analytical process with time-lapse confocal microscopy follow mitosis movements which Digital Volume Correlation. showed that these two different types differently divisions causing mainly uniaxial displacement, whereas ones involved multiaxial more one.
Language: Английский
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1Published: Oct. 30, 2024
Language: Английский
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0