Ubc9 overexpression and SUMO1 deficiency blunt inflammation after intestinal ischemia/reperfusion

Laboratory Investigation; a Journal of Technical Methods and Pathology
Jörn KarhausenWulf Paschen

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 a...Continue Reading

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Citations

Aug 21, 2019·Oxidative Medicine and Cellular Longevity·Xiyun BianXiaozhi Liu
Aug 17, 2021·Frontiers in Cardiovascular Medicine·Wei ZhaoJianhui Rong
Aug 25, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Zhihao LiuGuanwei Fan

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Datasets Mentioned

BETA
GSE96733

Methods Mentioned

BETA
scraping
electrophoresis
PCR
Profiler
transgenic
scrapings
dissect

Software Mentioned

R
Ingenuity Pathway Analysis ( IPA )
ImageJ
RT2 Profiler
GeneChip Operation Software

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