SGK1 mediates hypotonic challenge-induced proliferation in basilar artery smooth muscle cells via promoting CREB signaling pathway

Chen, Bao-Yi; Wang, Surong; Lu, Feng-Ting; Lv, Xiao‐Fei; Chen, Yuan; Ma, Ming; Guan, Yong‐Yuan

doi:10.1016/j.ejphar.2021.173997

Cited by 9 publications

(5 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SGK1 was subsequently found to play a critical role in the proliferation of cancer cells harboring PI3 kinase mutations ( 70 , 71 ). Knockdown of SGK1 impaired basilar smooth muscle cell progress from G0/G1 phase to S phase ( 72 ) and overexpression of SGK1 stimulated cultured colon cancer cell proliferation ( 73 ). SGK1 expression is elevated in colon cancer cells and in other cancers ( 74 ).…”

Section: Discussionmentioning

confidence: 99%

ROS signaling–induced mitochondrial Sgk1 expression regulates epithelial cell renewal

Liu

Rolling

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Many types of differentiated cells can reenter the cell cycle upon injury or stress. The underlying mechanisms are still poorly understood. Here, we investigated how quiescent cells are reactivated using a zebrafish model, in which a population of differentiated epithelial cells are reactivated under a physiological context. A robust and sustained increase in mitochondrial membrane potential was observed in the reactivated cells. Genetic and pharmacological perturbations show that elevated mitochondrial metabolism and ATP synthesis are critical for cell reactivation. Further analyses showed that elevated mitochondrial metabolism increases mitochondrial ROS levels, which induces Sgk1 expression in the mitochondria. Genetic deletion and inhibition of Sgk1 in zebrafish abolished epithelial cell reactivation. Similarly, ROS-dependent mitochondrial expression of SGK1 promotes S phase entry in human breast cancer cells. Mechanistically, SGK1 coordinates mitochondrial activity with ATP synthesis by phosphorylating F 1 F o -ATP synthase. These findings suggest a conserved intramitochondrial signaling loop regulating epithelial cell renewal.

show abstract

Section: Discussionmentioning

confidence: 99%

ROS signaling–induced mitochondrial Sgk1 expression regulates epithelial cell renewal

Liu

Rolling

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Previous stroke studies have shown that survived resident microglia are important for the regulation of neuroin ammation and have an important neuroprotective potential by serving as an endogenous pool of neurotrophic and antiapoptotic molecules such as IGF-1 50,51 . Our previous study showed that VRAC could regulate cell proliferation, apoptosis and survival through the Cl − -sensitive SGK1 signaling pathway 24,52 .…”

Section: Discussionmentioning

confidence: 99%

Activation of Swell1 in microglia suppresses neuroinflammation and reduces brain damage in ischemic stroke

Chen

Xie

Shi

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Neuroinflammation and immune responses mediated by microglia are associated with brain injury after ischemic stroke, and it is novel that Cl− movement and Cl-sensitive signal pathways have been shown to be implicated in the survival and switch of inflammation patterns of immune cells. Swell1, one of the components of Volume-regulated Cl− currents (VRAC) is considered to be the main channels mediating Cl− efflux from nerves cells. However, the role of Swell11 in ischemia-induced inflammation and the effect of Swell1 on the inflammation patterns switch of microglia remain unknown. Methods Whole-cell patch clamp recordings was used to examine Swell1-mediated VRAC in BV2 cells. In vivo and vitro studies comparing EGFP and Swell1 conditional knock-in mice were performed to determine the role of microglia Swell1 on inflammation and brain injury after ischemic stroke. In vitro experiments to further explored the mechanism of microglia Swell1 in regulating neuroinflammation. Results Our data showed that knockdown or overexpression of Swell1 in cultured BV2 cells inhibited or increased hypotonic-activated Cl− currents, respectively, and these changes were completely blocked by the VRAC inhibitor DCPIB. Swell1 conditional knock-in mice promoted microglial survival in the lesion region, leading to reductions in neural cell apoptosis, infarction size and neurological deficits following transient middle cerebral artery occlusion (tMCAO). Using gene manipulating technique and pharmacological inhibitors, we further revealed that Swell1 opening led to SGK1 (a Cl−-sensitive kinase)-mediated activation of FOXO3a/CREB as well as WNK1 (another Cl−-sensitive kinase)-mediated SPAK/OSR1-CCCs activation, which promoted microglial survival and M2 polarization, thereby attenuating inflammation and ischemic brain injury. Conclusion Our results demonstrated that Swell1 is an essential component of microglia VRAC and its activation protects against ischemic brain injury through promoting microglial survival and M2 polarization, which provides new a new orientation for the treatment of ischemic stroke and other neurological diseases associated with inflammation.

show abstract

“…SGK1 was subsequently found to play a critical role in proliferation of cancer cells harboring PI3 kinase mutations (Castel et al, 2016; Orlacchio et al, 2017). Knockdown of SGK1 impaired basilar smooth muscle cell progress from G0/G1 phase to S phase (Chen et al, 2021) and overexpression of SGK1 stimulates cultured colon cancer cell proliferation (Liang et al, 2017). SGK1 expression is elevated in colon cancer cells and in other cancers (Lang et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

ROS signaling-induced mitochondrial Sgk1 regulates epithelial cell plasticity

Liu

Rolling

et al. 2022

Preprint

View full text Add to dashboard Cite

Many types of differentiated cells can reenter the cell cycle upon injury or stress. The mechanisms underlying this cell plasticity are still poorly understood. Here we investigated cell plasticity regulation using a zebrafish model, in which a population of differentiated epithelial cells are reactivated under a physiological context. We observed a robust and sustained increase in mitochondrial membrane potential in reactivated cells. Genetic and pharmacological perturbations show that elevated mitochondrial metabolism and ATP synthesis are critical for cell reactivation. Elevated mitochondrial metabolism increases mitochondrial ROS levels, which induces Sgk1 expression in the mitochondria. Deletion and inhibition of Sgk1 in zebrafish abolished cell reactivation. Similarly, ROS-dependent mitochondrial expression of SGK1 promotes S phase entry in human breast cancer cells. Mechanistically, Sgk1 coordinates mitochondrial activity with ATP synthesis by modulating F1Fo-ATP synthase phosphorylation. These findings suggest a conserved intramitochondrial signaling loop regulating epithelial cell renewal.

show abstract

SGK1 mediates hypotonic challenge-induced proliferation in basilar artery smooth muscle cells via promoting CREB signaling pathway

Cited by 9 publications

References 45 publications

ROS signaling–induced mitochondrial Sgk1 expression regulates epithelial cell renewal

ROS signaling–induced mitochondrial Sgk1 expression regulates epithelial cell renewal

Activation of Swell1 in microglia suppresses neuroinflammation and reduces brain damage in ischemic stroke

ROS signaling-induced mitochondrial Sgk1 regulates epithelial cell plasticity

Contact Info

Product

Resources

About