2017
DOI: 10.18632/aging.101179
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Abstract: Loss of cell polarity impairs organ development and function; it can also serve as one of the first triggers for oncogenesis. In 2006-2007 two groups simultaneously reported the existence of a special pathway for maintaining epithelial polarity in the face of environmental stressors. In this pathway, AMPK, a key sensor of metabolic stress stabilizes tight junctions, preserves cell polarity, and thereby, maintains epithelial barrier functions. Accumulating evidence since has shown that pharmacologic activation … Show more

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Cited by 7 publications
(7 citation statements)
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References 104 publications
(134 reference statements)
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“…In addition, it was demonstrated recently that GIRDIN acts as an effector of AMP-activated protein kinase (AMPK) under energetic stress to maintain tight junction function [39]. Of note, these two functions are not shared by fly Girdin [58,59], and were thus acquired by GIRDIN during evolution to fulfill specialized functions. In contrast, our discovery of the Girdin-dependent inhibition of aPKC reveals a core mechanism contributing to epithelial cell polarization from flies to humans.…”
Section: Discussionmentioning
confidence: 99%
“…In addition, it was demonstrated recently that GIRDIN acts as an effector of AMP-activated protein kinase (AMPK) under energetic stress to maintain tight junction function [39]. Of note, these two functions are not shared by fly Girdin [58,59], and were thus acquired by GIRDIN during evolution to fulfill specialized functions. In contrast, our discovery of the Girdin-dependent inhibition of aPKC reveals a core mechanism contributing to epithelial cell polarization from flies to humans.…”
Section: Discussionmentioning
confidence: 99%
“…In more recent work, treatment with rapamycin, which inhibits Akt-dependent mechanistic Target of Rapamycin (mTOR) signaling, maintained epithelial barrier integrity and extended lifespan in D. melanogaster independently of any changes in the gut microbiota (Schinaman et al, 2019). In mammals, AMPK is required for regulation of polarity of hepatocytes and other epithelial cell types as well as tight junction and barrier integrity through increased mitochondrial fusion and biogenesis (Treyer and Müsch, 2013;Kang et al, 2016;Ghosh, 2017). Successful P.…”
Section: Mitochondrial Function Controls Epithelial Barrier Integritymentioning
confidence: 99%
“…Metformin may also improve gut barrier function through tightening of gut epithelial cell junctions via the AMP-activated protein kinase (AMPK) pathway [77]. Compared to other anti-diabetic drugs, metformin is associated with decreased risk for sepsis, which supports this potential therapeutic effect of metformin [78].…”
Section: Potential Therapeutic Interventionsmentioning
confidence: 99%