ArticleThe Journal of biological chemistry2009
Strain-induced proliferation requires the phosphatidylinositol 3-kinase/AKT/glycogen synthase kinase pathway.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Age-Dependent Alterations in Intestinal Barrier Function: Involvement of Microbiota and TLR4 Signaling.Biology · 2026Article
- Upregulation of the microRNA rno-miR-146b-5p may be involved in the development of intestinal injury through inhibition of Kruppel-like factor 4 in intestinal sepsis.Bioengineered · 2020Article
- Review
- Article
- Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Cyclic stretch disrupts apical junctional complexes in Caco-2 cell monolayers by a JNK-2-, c-Src-, and MLCK-dependent mechanism.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Periostin induces intracellular cross-talk between kinases and hyaluronan in atrioventricular valvulogenesis.The Journal of biological chemistry · 2014Article
- Article
- Genetic and bioinformatic analyses of the expression and function of PI3K regulatory subunit PIK3R3 in an Asian patient gastric cancer library.BMC medical genomics · 2012Article
- Role of RhoA and its effectors ROCK and mDia1 in the modulation of deformation-induced FAK, ERK, p38, and MLC motogenic signals in human Caco-2 intestinal epithelial cells.American journal of physiology. Cell physiology · 2011Article
- ILK mediates the effects of strain on intestinal epithelial wound closure.American journal of physiology. Cell physiology · 2011Article
- Novel avenues of drug discovery and biomarkers for diabetes mellitus.Journal of clinical pharmacology · 2011Review
- Schlafen 3 induction by cyclic strain regulates intestinal epithelial differentiation.American journal of physiology. Gastrointestinal and liver physiology · 2010Article
- Pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC1HOP1 receptor activation coordinates multiple neurotrophic signaling pathways: Akt activation through phosphatidylinositol 3-kinase gamma and vesicle endocytosis for neuronal survival.The Journal of biological chemistry · 2010Article
- Oxidative stress: Biomarkers and novel therapeutic pathways.Experimental gerontology · 2010Review
- Diabetes mellitus: channeling care through cellular discovery.Current neurovascular research · 2010Article
- Oscillatory flow-induced proliferation of osteoblast-like cells is mediated by alphavbeta3 and beta1 integrins through synergistic interactions of focal adhesion kinase and Shc with phosphatidylinositol 3-kinase and the Akt/mTOR/p70S6K pathway.The Journal of biological chemistry · 2010Article
- FoxO3a governs early microglial proliferation and employs mitochondrial depolarization with caspase 3, 8, and 9 cleavage during oxidant induced apoptosis.Current neurovascular research · 2009Article
- Erythropoietin, forkhead proteins, and oxidative injury: biomarkers and biology.TheScientificWorldJournal · 2009Review
- The vitamin nicotinamide: translating nutrition into clinical care.Molecules (Basel, Switzerland) · 2009Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The intestinal epithelium is repetitively deformed by shear, peristalsis, and villous motility. Such repetitive deformation stimulates the proliferation of intestinal epithelial cells on collagen or laminin substrates via ERK, but the upstream mediators of this effect are poorly understood. We hypothesized that the phosphatidylinositol 3-kinase (PI3K)/AKT cascade mediates this mitogenic effect. PI3K, AKT, and glycogen synthase kinase-3beta (GSK-3beta) were phosphorylated by 10 cycles/min strain at an average 10% deformation, and pharmacologic blockade of these molecules or reduction by small interfering RNA (siRNA) prevented the mitogenic effect of strain in Caco-2 or IEC-6 intestinal epithelial cells. Strain MAPK activation required PI3K but not AKT. AKT isoform-specific siRNA transfection demonstrated that AKT2 but not AKT1 is required for GSK-3beta phosphorylation and the strain mitogenic effect. Furthermore, overexpression of AKT1 or an AKT chimera including the PH domain and hinge region of AKT2 and the catalytic domain and C-tail of AKT1 prevented strain activation of GSK-3beta, but overexpression of AKT2 or a chimera including the PH domain and hinge region of AKT1 and the catalytic domain and C-tail of AKT2 did not. These data delineate a role for PI3K, AKT2, and GSK-3beta in the mitogenic effect of strain. PI3K is required for both ERK and AKT2 activation, whereas AKT2 is sequentially required for GSK-3beta. Furthermore, AKT2 specificity requires its catalytic domain and tail region. Manipulating this pathway may prevent mucosal atrophy and maintain the mucosal barrier in conditions such as ileus, sepsis, and prolonged fasting when peristalsis and villous motility are decreased and the mucosal barrier fails.
Indexed as
Identifiers
What OpenQuestion holds
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.