ArticlePhysiological reports2016
Intravital imaging of mouse urothelium reveals activation of extracellular signal-regulated kinase by stretch-induced intravesical release of ATP.
Article in Physiological reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Urothelial collective-gliding response acts as a toll-like receptor 4-associated defense mechanism.iScience · 2025Article
- ATP dynamics as a predictor of future podocyte structure and function after acute ischemic kidney injury in female mice.Nature communications · 2024Article
- Emerging roles and mechanisms of ERK pathway mechanosensing.Cellular and molecular life sciences : CMLS · 2023Review
- Article
- Effect of the neuropathic pain receptor P2X3 on bladder function induced by intraperitoneal injection of cyclophosphamide (CYP) in interstitial cystitis rats.Translational andrology and urology · 2022Article
- Article
- Article
- Spatiotemporal ATP Dynamics during AKI Predict Renal Prognosis.Journal of the American Society of Nephrology : JASN · 2020Article
- The Urothelium: Life in a Liquid Environment.Physiological reviews · 2020Review
- Biliverdin Reductase-A Deficiency Brighten and Sensitize Biliverdin-binding Chromoproteins.Cell structure and function · 2020Article
- Experimental pathology by intravital microscopy and genetically encoded fluorescent biosensors.Pathology international · 2020Review
- Solid stress, competition for space and cancer: The opposing roles of mechanical cell competition in tumour initiation and growth.Seminars in cancer biology · 2020Review
- Cancer invasion into musculature: Mechanics, molecules and implications.Seminars in cell & developmental biology · 2019Review
- Competition for Space Induces Cell Elimination through Compaction-Driven ERK Downregulation.Current biology : CB · 2019Article
- Modulation of lower urinary tract smooth muscle contraction and relaxation by the urothelium.Naunyn-Schmiedeberg's archives of pharmacology · 2018Review
- Circadian coordination of ATP release in the urothelium via connexin43 hemichannels.Scientific reports · 2018Article
- Non-invasive voiding assessment in conscious mice.Bladder (San Francisco, Calif.) · 2018Article
- Article
- Intravital imaging of mouse urothelium reveals activation of extracellular signal-regulated kinase by stretch-induced intravesical release of ATP.Physiological reports · 2016Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To better understand the roles played by signaling molecules in the bladder, we established a protocol of intravital imaging of the bladder of mice expressing a Förster/fluorescence resonance energy transfer (FRET) biosensor for extracellular signal-regulated kinase (ERK), which plays critical roles not only in cell growth but also stress responses. With an upright two-photon excitation microscope and a vacuum-stabilized imaging window, cellular ERK activity was visualized in the whole bladder wall, from adventitia to urothelium. We found that bladder distention caused by elevated intravesical pressure (IVP) activated ERK in the urothelium, but not in the detrusor smooth muscle. When bladder distension was prevented, high IVP failed to activate ERK, suggesting that mechanical stretch, but not the high IVP, caused ERK activation. To delineate its molecular mechanism, the stretch-induced ERK activation was reproduced in an hTERT-immortalized human urothelial cell line (TRT-HU1) in vitro. We found that uniaxial stretch raised the ATP concentration in the culture medium and that inhibition of ATP signaling by apyrase or suramin suppressed the stretch-induced ERK activation in TRT-HU1 cells. In agreement with this in vitro observation, pretreatment with apyrase or suramin suppressed the high IVP-induced urothelial ERK activation in vivo. Thus, we propose that mechanical stretch induces intravesical secretion of ATP and thereby activates ERK in the urothelium. Our method of intravital imaging of the bladder of FRET biosensor-expressing mice should open a pathway for the future association of physiological stimuli with the activities of intracellular signaling networks.
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