ArticleLaboratory investigation; a journal of technical methods and pathology2018
Ubc9 overexpression and SUMO1 deficiency blunt inflammation after intestinal ischemia/reperfusion.
Article in Laboratory investigation; a journal of technical methods and pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Ubc9-mediated SUMOylation of Ninj1 alleviates inflammatory responses in hepatic ischaemia/reperfusion injury.Clinical and translational medicine · 2026Article
- ROS-SUMO Crosstalk in Oxidative Stress: Disease Mechanisms and Reproductive Health.Antioxidants (Basel, Switzerland) · 2026Review
- Impact of Diabetes on Oxidative Stress, Mitochondrial Function, and Neurological Outcomes Following Ischemic Stroke: A Sex-Based Experimental Analysis.Molecular neurobiology · 2025Article
- SUMOylation Regulates Neutrophil Phagocytosis and Migration.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Vagal stimulation ameliorates murine colitis by regulating SUMOylation.Science translational medicine · 2024Article
- Dexmedetomidine alleviates intestinal ischemia/reperfusion injury by modulating intestinal neuron autophagy and mitochondrial homeostasis via Nupr1 regulation.Molecular medicine (Cambridge, Mass.) · 2024Article
- SUMOylation at the crossroads of gut health: insights into physiology and pathology.Cell communication and signaling : CCS · 2024Review
- E3 ligase TRIM65 alleviates intestinal ischemia/reperfusion injury through inhibition of TOX4-mediated apoptosis.Cell death & disease · 2024Article
- SUMO2 rescues neuronal and glial cells from the toxicity of P301L Tau mutant.Frontiers in cellular neuroscience · 2024Article
- NRIP1 aggravates lung injury caused byAging · 2022Article
- JAK2/STAT3 inhibition attenuates intestinal ischemia-reperfusion injury via promoting autophagy: in vitro and in vivo study.Molecular biology reports · 2022Article
- Tofacitinib protects intestinal epithelial cells against oxygen-glucose deprivation/reoxygenation injury by inhibiting the JAK/STAT3 signaling pathway.Experimental and therapeutic medicine · 2021Article
- SUMO paralogue-specific functions revealed through systematic analysis of human knockout cell lines and gene expression data.Molecular biology of the cell · 2021Article
- SUMOylation as a Therapeutic Target for Myocardial Infarction.Frontiers in cardiovascular medicine · 2021Review
- SUMOylation Connects Cell Stress Responses and Inflammatory Control: Lessons From the Gut as a Model Organ.Frontiers in immunology · 2021Review
- Molecular Mechanisms Underlying Intestinal Ischemia/Reperfusion Injury: Bioinformatics Analysis and In Vivo Validation.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Zinc-Induced SUMOylation of Dynamin-Related Protein 1 Protects the Heart against Ischemia-Reperfusion Injury.Oxidative medicine and cellular longevity · 2019Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The intestinal epithelium constitutes a crucial defense to the potentially life-threatening effects of gut microbiota. However, due to a complex underlying vasculature, hypoperfusion and resultant tissue ischemia pose a particular risk to function and integrity of the epithelium. The small ubiquitin-like modifier (SUMO) conjugation pathway critically regulates adaptive responses to metabolic stress and is of particular significance in the gut, as inducible knockout of the SUMO-conjugating enzyme Ubc9 results in rapid intestinal epithelial disintegration. Here we analyzed the pattern of individual SUMO isoforms in intestinal epithelium and investigated their roles in intestinal ischemia/reperfusion (I/R) damage. Immunostaining revealed that epithelial SUMO2/3 expression was almost exclusively limited to crypt epithelial nuclei in unchallenged mice. However, intestinal I/R or overexpression of Ubc9 caused a remarkable enhancement of epithelial SUMO2/3 staining along the crypt-villus axis. Unexpectedly, a similar pattern was found in SUMO1 knockout mice. Ubc9 transgenic mice, but also SUMO1 knockout mice were protected from I/R injury as evidenced by better preserved barrier function and blunted inflammatory responses. PCR array analysis of microdissected villus-tip epithelia revealed a specific epithelial contribution to reduced inflammatory responses in Ubc9 transgenic mice, as key chemotactic signaling molecules such as IL17A were significantly downregulated. Together, our data indicate a critical role particularly of the SUMO2/3 isoforms in modulating responses to I/R and provide the first evidence that SUMO1 deletion activates a compensatory process that protects from ischemic damage.
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