Abnormal PTEN expression in portal hypertensive gastric mucosa: A key to impaired PI 3‐kinase/Akt activation and delayed injury healing?

Tsugawa, Kouji; Jones, Michael K.; Akahoshi, Tomohiko; Moon, Woo Sung; Maehara, Yoshihiko; Hashizume, Makoto; Sarfeh, I. James; Tarnawski, Andrzej S.

doi:10.1096/fj.02-1107fje

Cited by 22 publications

(24 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the mouse system and human cells (MEFs, HT1080, 293T 20 ), consistent significant effects have been observed in other cells and tissues, [21][22][23][24][25] (Table 1). Moorehead et al 22 observed that Egr1 is induced by and required for IGF-II-dependent induction of PTEN in the mouse mammary gland, an effect that is absent in Egr1-null mice.…”

Section: Ptensupporting

confidence: 64%

The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFβ1, PTEN, p53, and fibronectin

Bar-On

Adamson

Calogero³

et al. 2005

Cancer Gene Ther

326

281

View full text Add to dashboard Cite

Recent studies are reviewed indicating that the transcription factor early growth response-1 (Egr1) is a direct regulator of multiple tumor suppressors including TGFb1, PTEN, p53, and fibronectin. The downstream pathways of these factors display multiple nodes of interaction with each other, suggesting the existence of a functional network of suppressor factors that serve to maintain normal growth regulation and resist the emergence of transformed variants. Paradoxically, Egr1 is oncogenic in prostate cancer. In the majority of these cancers, PTEN or p53 is inactive. It is suggested that these defects in the suppressor network allow for the unopposed induction of TGFb1 and fibronectin, which favor transformation and survival of prostate tumor epithelial cells, and explain the role of Egr1 in prostate cancer. Egr1 is a novel and logical target for intervention by gene therapy methods, and targeting methods are discussed.

show abstract

Section: Ptensupporting

confidence: 64%

The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFβ1, PTEN, p53, and fibronectin

Bar-On

Adamson

Calogero³

et al. 2005

Cancer Gene Ther

326

281

View full text Add to dashboard Cite

show abstract

“…Importantly, we have observed that PI3K/Akt signaling in primary human lung epithelia occurs subsequent to PTEN inhibition and without further addition of agonists. Consistent with these observations, others have reported similar effects in cardiomyocytes during ischemia-reperfusion (39), corneal and skin epithelia (76), and gastric mucosal cells (65). Although activation of the PI3K/Akt pathway plays a role in facilitating epithelial repair consequent to PTEN inhibition, PTEN is pleiotropic by virtue of multiple downstream pathways directly affected by its phosphatase activity, and the importance of these other pathways remains unclear.…”

mentioning

confidence: 58%

PTEN inhibition improves wound healing in lung epithelia through changes in cellular mechanics that enhance migration

Mihai

Bao²,

Lai³

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

The phosphoinositide-3 kinase/Akt pathway is a vital survival axis in lung epithelia. We previously reported that inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a major suppressor of this pathway, results in enhanced wound repair following injury. However, the precise cellular and biomechanical mechanisms responsible for increased wound repair during PTEN inhibition are not yet well established. Using primary human lung epithelia and a related lung epithelial cell line, we first determined whether changes in migration or proliferation account for wound closure. Strikingly, we observed that cell migration accounts for the majority of wound recovery following PTEN inhibition in conjunction with activation of the Akt and ERK signaling pathways. We then used fluorescence and atomic force microscopy to investigate how PTEN inhibition alters the cytoskeletal and mechanical properties of the epithelial cell. PTEN inhibition did not significantly alter cytoskeletal structure but did result in large spatial variations in cell stiffness and in particular a decrease in cell stiffness near the wound edge. Biomechanical changes, as well as migration rates, were mediated by both the Akt and ERK pathways. Our results indicate that PTEN inhibition rapidly alters biochemical signaling events that in turn provoke alterations in biomechanical properties that enhance cell migration. Specifically, the reduced stiffness of PTEN-inhibited cells promotes larger deformations, resulting in a more migratory phenotype. We therefore conclude that increased wound closure consequent to PTEN inhibition occurs through enhancement of cell migration that is due to specific changes in the biomechanical properties of the cell.

show abstract

“…In portal hypertensive gastropathy (PHT), there is distorted microangioarchitecture and impaired angiogenesis in gastric mucosa in response to ethanol injury . Studies have demonstrated that PHT exhibits defects in signaling pathways such as Erk and PI3k/Akt and has overexpressed NOS resulting in high NO levels . Each of these abnormalities likely contributes to the impaired angiogenesis demonstrated as a consequence of PHT.…”

Section: Introductionmentioning

confidence: 99%

Angiogenesis in gastric mucosa: An important component of gastric erosion and ulcer healing and its impairment in aging

Tarnawski

Ahluwalia

Jones

2014

J of Gastro and Hepatol

View full text Add to dashboard Cite

Angiogenesis (also referred to as neovascularization-formation of new blood vessels from existing vessels) is a fundamental process essential for healing of tissue injury and ulcers because regeneration of blood microvessels is a critical requirement for oxygen and nutrient delivery to the healing site. This review article updates the current views on angiogenesis in gastric mucosa following injury and during ulcer healing, its sequential events, the underlying mechanisms, and the impairment of angiogenesis in aging gastric mucosa. We focus on the time sequence and ultrastructural features of angiogenesis, hypoxia as a trigger, role of vascular endothelial growth factor signaling (VEGF), serum response factor, Cox2 and prostaglandins, nitric oxide, and importin. Recent reports indicate that gastric mucosa of aging humans and experimental animals exhibits increased susceptibility to injury and delayed healing. Gastric mucosa of aging rats has increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin, and other non-steroidal antiinflammatory drugs because of structural and functional abnormalities including: reduced gastric mucosal blood flow, hypoxia, reduced expression of vascular endothelial growth factor and survivin, and increased expression of early growth response protein 1 (egr-1) and phosphatase and tensin homolog (PTEN). Until recently, postnatal neovascularization was assumed to occur solely through angiogenesis sprouting of endothelial cells and formation of new blood vessels from pre-existing blood vessels. New studies in the last decade have challenged this paradigm and indicate that in some tissues, including gastric mucosa, the homing of bone marrow-derived endothelial progenitor cells to the site of injury can also contribute to neovascularization by a process termed vasculogenesis.

show abstract

Abnormal PTEN expression in portal hypertensive gastric mucosa: A key to impaired PI 3‐kinase/Akt activation and delayed injury healing?

Cited by 22 publications

References 45 publications

The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFβ1, PTEN, p53, and fibronectin

The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFβ1, PTEN, p53, and fibronectin

PTEN inhibition improves wound healing in lung epithelia through changes in cellular mechanics that enhance migration

Angiogenesis in gastric mucosa: An important component of gastric erosion and ulcer healing and its impairment in aging

Contact Info

Product

Resources

About