ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2018
β-PIX plays an important role in regulation of intestinal epithelial restitution by interacting with GIT1 and Rac1 after wounding.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
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- Stabilization ofAmerican journal of physiology. Gastrointestinal and liver physiology · 2023Article
- miR-195 regulates intestinal epithelial restitution after wounding by altering actin-related protein-2 translation.American journal of physiology. Cell physiology · 2022Article
- TRPC1-mediated CaPhysiological reports · 2021Article
- Targeted intestinal deletion of Rho guanine nucleotide exchange factor 7, βPIX, impairs enterocyte proliferation, villus maturation, and mucosal defenses in mice.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- GPCRs, G Proteins, and Their Impact on β-cell Function.Comprehensive Physiology · 2020Review
- Quantitative proteomics reveals novel interaction partners of Rac1 in pancreatic β-cells: Evidence for increased interaction with Rac1 under hyperglycemic conditions.Molecular and cellular endocrinology · 2019Article
- miR-222 represses expression of zipcode binding protein-1 and phospholipase C-γ1 in intestinal epithelial cells.American journal of physiology. Cell physiology · 2019Article
- Effects of a synbiotic on the fecal microbiome and metabolomic profiles of healthy research cats administered clindamycin: a randomized, controlled trial.Gut microbes · 2019Article
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7 authors at 1 institution in 1 country.
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Abstract
Early gut mucosal restitution is a process by which intestinal epithelial cells (IECs) migrate over the wounded area, and its defective regulation occurs commonly in various critical pathological conditions. This rapid reepithelialization is mediated by different activating small GTP-binding proteins, but the exact mechanism underlying this process remains largely unknown. Recently, it has been reported that interaction between p21-activated kinase-interacting exchange factor (β-PIX) and G protein-coupled receptor kinase-interacting protein 1 (GIT1) activates small GTPases and plays an important role in the regulation of cell motility. Here, we show that induced association of β-PIX with GIT1 is essential for the stimulation of IEC migration after wounding by activating Rac1. Levels of β-PIX and GIT1 proteins and their association in differentiated IECs (line of IEC-Cdx2L1) were much higher than those observed in undifferentiated IECs (line of IEC-6), which was associated with an increase in IEC migration after wounding. Decreased levels of endogenous β-PIX by its gene-silencing destabilized β-PIX/GIT1 complexes, repressed Rac1 activity and inhibited cell migration over the wounded area. In contrast, ectopic overexpression of β-PIX increased the levels of β-PIX/GIT1 complexes, stimulated Rac1 activity, and enhanced intestinal epithelial restitution. Increased levels of cellular polyamines also stimulated β-PIX/GIT1 association, increased Rac1 activity, and promoted the epithelial restitution. Moreover, polyamine depletion decreased cellular abundances of β-PIX/GIT1 complex and repressed IEC migration after wounding, which was rescued by ectopic overexpression of β-PIX or GIT1. These results indicate that β-PIX/GIT1/Rac1 association is necessary for stimulation of IEC migration after wounding and that this signaling pathway is tightly regulated by cellular polyamines. NEW & NOTEWORTHY Our current study demonstrates that induced association of β-PIX with GIT1 is essential for the stimulation of intestinal epithelial restitution by activating Rac1, and this signaling pathway is tightly regulated by cellular polyamines.
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