ArticleThe American journal of pathology2010
Mammalian target of rapamycin (mTOR) induces proliferation and de-differentiation responses to three coordinate pathophysiologic stimuli (mechanical strain, hypoxia, and extracellular matrix remodeling) in rat bladder smooth muscle.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 47 citations in OpenAlex.
- Characterization of global and region-specific transcriptomic alterations in the bladder following acute partial bladder outlet obstruction in female mini-swine.Physiological reports · 2026Article
- Dedifferentiated fat cells: current applications and future directions in regenerative medicine.Stem cell research & therapy · 2023Review
- Article
- The matrix metalloproteinase 7 (MMP7) links Hsp90 chaperone with acquired drug resistance and tumor metastasis.Cancer reports (Hoboken, N.J.) · 2022Article
- Inhibition of DNA methylation during chronic obstructive bladder disease (COBD) improves function, pathology and expression.Scientific reports · 2021Article
- mTOR Signaling in Pulmonary Vascular Disease: Pathogenic Role and Therapeutic Target.International journal of molecular sciences · 2021Review
- Non-invasive voiding assessment in conscious mice.Bladder (San Francisco, Calif.) · 2018Article
- hASC and DFAT, Multipotent Stem Cells for Regenerative Medicine: A Comparison of Their Potential Differentiation In Vitro.International journal of molecular sciences · 2017Article
- MicroRNA-184 promotes differentiation of the retinal pigment epithelium by targeting the AKT2/mTOR signaling pathway.Oncotarget · 2016Article
- Current challenges in dedifferentiated fat cells research.Organogenesis · 2016Review
- The interplay of extracellular matrix and microbiome in urothelial bladder cancer.Nature reviews. Urology · 2016Review
- Uropathogenic E. coli (UPEC) Infection Induces Proliferation through Enhancer of Zeste Homologue 2 (EZH2).PloS one · 2016Article
- Dedifferentiated fat cells: A cell source for regenerative medicine.World journal of stem cells · 2015Review
- T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage.BioMed research international · 2015Review
- Assessment of local structural disorders of the bladder wall in partial bladder outlet obstruction using polarized light imaging.Biomedical optics express · 2014Article
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- Article
- mTOR-mediated dedifferentiation of the retinal pigment epithelium initiates photoreceptor degeneration in mice.The Journal of clinical investigation · 2011Article
- The bladder extracellular matrix. Part I: architecture, development and disease.Nature reviews. Urology · 2009Review
- Adaptive inflammatory microenvironment for cell-based regeneration in ischemic cardiovascular disease.OrganogenesisArticle
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Maladaptive bladder muscle overgrowth and de-differentiation in human bladder obstructive conditions is instigated by coordinate responses to three stimuli: mechanical strain, tissue hypoxia, and extracellular matrix remodeling.( 1,2) Pathway analysis of genes induced by obstructive models of injury in bladder smooth muscle cells (BSMCs) identified a mammalian target of rapamycin (mTOR)-specific inhibitor as a potential pharmacological inhibitor. Strain-induced mTOR-specific S6K activation segregated differently from ERK1/2 activation in intact bladder ex vivo. Though rapamycin's antiproliferative effects in vascular smooth muscle cells are well known, its effects on BSMCs were previously unknown. Rapamycin significantly inhibited proliferation of BSMCs in response to mechanical strain, hypoxia, and denatured collagen. Rapamycin inhibited S6K at mTOR-sensitive phosphorylation sites in response to strain and hypoxia. Rapamycin also supported smooth muscle actin expression in response to strain or hypoxia-induced de-differentiation. Importantly, strain plus hypoxia synergistically augmented mTOR-dependent S6K activation, Mmp7 expression and proliferation. Forced expression of wild-type and constitutively active S6K resulted in loss of smooth muscle actin expression. Decreased smooth muscle actin, increased Mmp7 levels and mTOR pathway activation during in vivo partial bladder obstruction paralleled our in vitro studies. These results point to a coordinate role for mTOR in BSMCs responses to the three stimuli and a potential new therapeutic target for myopathic bladder disease.
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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.