ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2012
RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 28 citations in OpenAlex.
- Advances in Understanding Calcium Sensitization in Gastrointestinal Smooth Muscles: Pathways, Interstitial Cells, and Disease.Journal of neurogastroenterology and motility · 2026Review
- 3D spheroids versus 2D-cultured human adipose stem cells to generate smooth muscle cells in an internal anal sphincter-targeting cryoinjured mouse model.Stem cell research & therapy · 2024Article
- A novel intramuscular Interstitial Cell of Cajal is a candidate for generating pacemaker activity in the mouse internal anal sphincter.Scientific reports · 2020Article
- Rhythmic calcium transients in smooth muscle cells of the mouse internal anal sphincter.Neurogastroenterology and motility · 2020Article
- Downregulation of thromboxane A2 and angiotensin II type 1 receptors associated with aging-related decrease in internal anal sphincter tone.Scientific reports · 2019Article
- Control of Motility in the Internal Anal Sphincter.Journal of neurogastroenterology and motility · 2019Article
- Comparison of inhibitory neuromuscular transmission in the Cynomolgus monkey IAS and rectum: special emphasis on differences in purinergic transmission.The Journal of physiology · 2018Article
- In vivo magnetofection: a novel approach for targeted topical delivery of nucleic acids for rectoanal motility disorders.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Rho GTPases as therapeutic targets in cancer (Review).International journal of oncology · 2017Review
- Role of differentially expressed microRNA-139-5p in the regulation of phenotypic internal anal sphincter smooth muscle tone.Scientific reports · 2017Article
- Ca2+/calmodulin/MLCK pathway initiates, and RhoA/ROCK maintains, the internal anal sphincter smooth muscle tone.American journal of physiology. Gastrointestinal and liver physiology · 2017Article
- Aging-associated changes in microRNA expression profile of internal anal sphincter smooth muscle: Role of microRNA-133a.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Calcium Sensitization Mechanisms in Gastrointestinal Smooth Muscles.Journal of neurogastroenterology and motility · 2016Review
- The molecular basis of the genesis of basal tone in internal anal sphincter.Nature communications · 2016Article
- Role of microRNAs in gastrointestinal smooth muscle fibrosis and dysfunction: novel molecular perspectives on the pathophysiology and therapeutic targeting.American journal of physiology. Gastrointestinal and liver physiology · 2016Review
- Bimodal effect of oxidative stress in internal anal sphincter smooth muscle.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Nature of extracellular signal that triggers RhoA/ROCK activation for the basal internal anal sphincter tone in humans.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Role of SM22 in the differential regulation of phasic vs. tonic smooth muscle.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- 2D DIGE Does Not Reveal all: A Scotopic Report Suggests Differential Expression of a Single "Calponin Family Member" Protein for Tetany of Sphincters!Frontiers in medicine · 2015Review
- Heme oxygenase-1 upregulation modulates tone and fibroelastic properties of internal anal sphincter.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10(-8) to 10(-4) M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC(20) in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC(20), before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment.
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Registered trials
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.