ArticlePloS one2017
Diabetes-induced oxidative stress mediates upregulation of RhoA/Rho kinase pathway and hypercontractility of gastric smooth muscle.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 32 citations in OpenAlex.
- Neuroprotective effect of ripasudil on retinal ganglion cells via an antioxidative mechanism.Japanese journal of ophthalmology · 2025Article
- The RAGE Inhibitor TTP488 (Azeliragon) Improves Diabetic Bladder Dysfunction in Leptin-Deficient Obese Mice.Antioxidants (Basel, Switzerland) · 2025Article
- Oxidative stress in asthma pathogenesis: mechanistic insights and implications for airway smooth muscle dysfunction.Cell and tissue research · 2025Review
- Unmasking Gastroparesis in Diabetes During Ramadan: Challenges and Management Strategies.Journal of clinical medicine · 2025Review
- Sex-specific epigenetics drive low GPER expression in gastrointestinal smooth muscles in type 2 diabetic mice.Scientific reports · 2024Article
- Gastroparesis might not be uncommon in patients with diabetes mellitus in a real-world clinical setting: a cohort study.BMC gastroenterology · 2024Article
- Gene Networks of Hyperglycemia, Diabetic Complications, and Human Proteins Targeted by SARS-CoV-2: What Is the Molecular Basis for Comorbidity?International journal of molecular sciences · 2022Article
- Insight Into Rho Kinase Isoforms in Obesity and Energy Homeostasis.Frontiers in endocrinology · 2022Review
- Review - Nutraceuticals Can Target Asthmatic Bronchoconstriction: NADPH Oxidase-Dependent Oxidative Stress, RhoA and Calcium Dynamics.Journal of asthma and allergy · 2021Review
- Role of sex hormones and their receptors on gastric Nrf2 and neuronal nitric oxide synthase function in an experimental hyperglycemia model.BMC gastroenterology · 2020Article
- Rapid gastric emptying in diabetes mellitus: Pathophysiology and clinical importance.Journal of diabetes and its complications · 2019Review
- The Role of MicroRNAs in Diabetes-Related Oxidative Stress.International journal of molecular sciences · 2019Review
- Diabetic Gastroparesis.Endocrine reviews · 2019Review
- GC/MS-based metabolomics strategy to analyze the effect of exercise intervention in diabetic rats.Endocrine connections · 2019Article
- Progressive Decrease in Coronary Vascular Function Associated With Type 2 Diabetic Heart Disease.Frontiers in physiology · 2018Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The pathogenesis of diabetes-associated motility disorders are multifactorial and attributed to abnormalities in extrinsic and intrinsic innervation, and a decrease in the number of interstitial cells of Cajal, and nNOS expression and activity. Here we studied the effect of hyperglycemia on smooth muscle function. Using smooth muscles from the fundus of ob/ob mice and of wild type (WT) mice treated with 30 mM glucose (HG), we identified the molecular mechanism by which hyperglycemia upregulates RhoA/Rho kinase pathway and muscle contraction. RhoA expression, Rho kinase activity and muscle contraction were increased, while miR-133a expression was decreased in smooth muscle of ob/ob mice and in smooth muscle treated with HG. Intraperitoneal injections of pre-miR-133a decreased RhoA expression in WT mice and reversed the increase in RhoA expression in ob/ob mice. Intraperitoneal injections of antagomiR-133a increased RhoA expression in WT mice and augmented the increase in RhoA expression in ob/ob mice. The effect of pre-miR-133a or antagomiR-133a in vitro in smooth muscle treated with HG was similar to that obtained in vivo, suggesting that the expression of RhoA is negatively regulated by miR-133a and a decrease in miR-133a expression in diabetes causes an increase in RhoA expression. Oxidative stress (levels of reactive oxygen species and hydrogen peroxide, and expression of superoxide dismutase 1 and NADPH oxidase 4) was increased in smooth muscle of ob/ob mice and in HG-treated smooth muscle. Treatment of ob/ob mice with N-acetylcysteine (NAC) in vivo or addition of NAC in vitro to HG-treated smooth muscle reversed the effect of glucose on the expression of miR-133a and RhoA, Rho kinase activity and muscle contraction. NAC treatment also reversed the decrease in gastric emptying in ob/ob mice. We conclude that oxidative stress in diabetes causes a decrease in miR-133a expression leading to an increase in RhoA/Rho kinase pathway and muscle contraction.
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