PI3K/Akt Signaling Pathway in the Basolateral Amygdala Mediates the Rapid Antidepressant-like Effects of Trefoil Factor 3

Shi, Haishui; Zhu, Weili; Liu, Jian-Feng; Luo, Yunping; Si, Jijian; Wang, Shenjun; Xue, Yan-Xue; Ding, Zhixia; Shi, Jie; Lü, Lin

doi:10.1038/npp.2012.131

Cited by 92 publications

(81 citation statements)

References 68 publications

(80 reference statements)

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“…The effects of ITF are transmitted to signaling cascades by still unknown adaptor proteins. Despite the absence of an identified cell surface receptor for ITF, ITF can act through the EGFR to activate several downstream effector pathways, including ERK1/2, Jun N-terminal kinase, and PI3K signal (15,32). In the present study, the results of western blotting (Fig.…”

Section: Discussionmentioning

confidence: 56%

“…In addition, these data indicated that ITF induces a dose-and time-dependent increase in Akt kinase activity of treated GES-1 cells. The downstream regulatory signaling pathway of ITF, the PI3K/Akt signaling pathway as an intracellular signal transducer plays a vital role in regulating cell survival, proliferation, migration and apoptosis (12,13,(32)(33)(34)(35)(36). In this study, the results indicated that PI3K/Akt signaling pathway participate in the regulation of ITF in GES-1 cell proliferation and migration in vitro.…”

Section: Discussionmentioning

confidence: 82%

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Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage

Sun

Yang

et al. 2014

International Journal of Oncology

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Abstract.Intestinal trefoil factor (ITF, also named as trefoil factor 3, TFF3) is a member of the TFF-domain peptide family, which plays an essential role in the regulation of cell survival, cell migration and maintains mucosal epithelial integrity in the gastrointestinal tract. However, the underlying mechanisms and associated molecules remain unclear. The aim of this study was to explore the protective effects of ITF on gastric mucosal epithelium injury and its possible molecular mechanisms of action. In the present study, we show that ITF was able to promote the proliferation and migration of GES-1 cells via a mechanism that involves the PI3K/Akt signaling pathway. Western blot results indicated that ITF induced a dose-and time-dependent increase in the Akt signaling pathway. ITF also plays an essential role in the restitution of GES-1 cell damage induced by lipopolysaccharide (LPS). LPS induced the apoptosis of GES-1 cells, decreased cell viability significantly (P<0.01) and led to epithelial tight junction damage, which is attenuated via ITF treatment. The protective effect of ITF on the integrity of GES-1 was abrogated by inhibition of the PI3K/Akt pathway. Taken together, our results demonstrate that ITF promotes the proliferation and migration of gastric mucosal epithelial cells and preserves gastric mucosal epithelial integrity after damage is mediated by activation of the PI3K/Akt signaling pathway. This study suggested that the PI3K/Akt pathway could act as a key intracellular pathway in the gastric mucosal epithelium that may serve as a therapeutic target to preserve epithelial integrity during injury.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 82%

Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage

Sun

Yang

et al. 2014

International Journal of Oncology

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“…The neuronal synthesis of Tff3 could explain various behavioral effects, e.g., dose dependent anxiolytic and anxiogenic effects after injections into the rat amygdala [13], effects on object recognition memory [24], and anti-depressant-like effects [25]. Additionally, Tff3-deficient mice showed differences in their motoric skills when compared with wild type animals [26].…”

Section: Discussionmentioning

confidence: 99%

Tff3 is Expressed in Neurons and Microglial Cells

Stellmacher

Znalesniak

et al. 2014

Cell Physiol Biochem

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Background/Aims: The trefoil factor family (TFF) peptide TFF3 is typically secreted by mucous epithelia, but is also expressed in the immune system and the brain. It was the aim of this study to determine the cerebral cell types which express Tff3. Methods: Primary cultures from rat embryonic or neonatal cerebral cortex and hippocampus, respectively, were studied by means of RT-PCR and immunofluorescence. Moreover, Tff3 expression was localized by immunocytochemistry in sections of adult rat cerebellum. Results: Tff3 transcripts were detectable in neural cultures of both the cortex and the hippocampus as well as in glial cell-enriched cultures. Tff3 peptide co-localized with Map2 indicating an expression in neurons in vitro. The neuronal expression was confirmed by immunofluorescence studies of adult rat cerebellum. Furthermore, Tff3 peptide showed also a clear co-localization with Iba-1 in vitro typical of activated microglial cells. Conclusion: The neuronal expression of Tff3 is in line with a function of a typical neuropeptide influencing, e.g., fear, memory, depression and motoric skills. The expression in activated microglial cells, which is demonstrated here for the first time, points towards a possible function for Tff3 in immune reactions in the CNS. This opens a plethora of additional possible functions for Tff3 including synaptic plasticity and cognition as well as during neuroinflammatory diseases and psychiatric disorders.

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“…Sucrose preference is considered to provide an index of anhedonia (Shi et al, 2012;Warner-Schmidt & Duman, 2008). The rats were trained to adapt to a 1% sucrose solution (w/v) for 48 hr at the beginning F I G U R E 1 (a) Flow diagram of experiment.…”

Section: Sucrose Preference Testmentioning

confidence: 99%

Short‐ and long‐term antidepressant effects of ketamine in a rat chronic unpredictable stress model

et al. 2017

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PI3K/Akt Signaling Pathway in the Basolateral Amygdala Mediates the Rapid Antidepressant-like Effects of Trefoil Factor 3

Cited by 92 publications

References 68 publications

Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage

Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage

Tff3 is Expressed in Neurons and Microglial Cells

Short‐ and long‐term antidepressant effects of ketamine in a rat chronic unpredictable stress model

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