Out with the bad: Studying autophagy to fight infectious disease

Shaffer, Leah

doi:10.1038/nm0416-334

Cited by 2 publications

(2 citation statements)

References 10 publications

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“…In this study, we uncovered elevated b-arr1 in the procession of liver fibrosis by using the tissues of patients with liver fibrosis and 2 distinct hepatic fibrosis models either induced by CCl 4 or by DMN in b-arr1-WT and b-arr1-KO littermates, and b-arr1 promoted the activation of autophagy in both hepatocytes and HSCs, which finally enhanced the progression of liver fibrosis via regulating Snail-mediated hepatocyte compensatory proliferation and HSC growth with activation. Autophagy has been implicated in mesenchymal cell activation and parenchymal cell homeostatic preservation in liver fibrosis (22,25). With the detection of the autophagic markers LC3 and BECN1 (40), we found that autophagy was induced dramatically in both patients with liver fibrosis and mice liver fibrotic models, and targeted deletion of b-arr1 inhibited the upregulation of autophagic proteins in mice.…”

Section: Discussionmentioning

confidence: 99%

“…Autophagy is an evolutionarily conserved process that targets cytosolic material and organelles to lysosomes to be degraded for survival, development, differentiation, and homeostasis (21,22), whereas dysfunctions in autophagy have been associated with lots of pathologies, including colitis, cancerogenesis, liver diseases, and so on (1,22). HSC activation in liver fibrosis is always associated with the happening of autophagy, including a marked increase in autophagic vacuoles and autophagic flux (23,24).…”

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confidence: 99%

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β‐Arrestin1 enhances liver fibrosis through autophagy‐mediated Snail signaling

Tan

et al. 2018

FASEB j.

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GPCR mediator β-arrestins (β-arr1 and β-arr2) regulate a variety of physiologic and pathologic processes, including hepatocellular carcinogenesis. However, the role of β-arrestins in liver fibrosis remains unknown. β-arr1, but not β-arr2, was upregulated in liver fibrotic tissues in both humans and mice; moreover, autophagy was increased. β-arr1 deficiency or autophagic inhibitor 3-methyladenine (3-MA) significantly blocked autophagy and downregulated liver fibrosis. Furthermore, β-arr1 enhanced hepatocyte compensatory proliferation, and hepatic stellate cell growth with activation via autophagy resulted in liver fibrosis. In the fibrosis, β-arr1 promoted nuclear translocation of Snail by downregulation of glycogen synthase kinase-3β, and the nuclear translocation of Snail was abrogated either by β-arr1 deficiency or by 3-MA. These results suggest that β-arr1 promotes liver fibrosis via autophagy-mediated Snail signaling, and β-arr1 may be a therapeutic target for liver fibrosis.-Tan, S., Lu, Y., Xu, M., Huang, X., Liu, H., Jiang, J., Wu, B. β-Arrestin1 enhances liver fibrosis through autophagy-mediated Snail signaling.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

β‐Arrestin1 enhances liver fibrosis through autophagy‐mediated Snail signaling

Tan

et al. 2018

FASEB j.

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Fas/FasL mediates NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to drive liver fibrosis

et al. 2021

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Fas/Fas ligand (FasL)-mediated cell apoptosis involves a variety of physiological and pathological processes including chronic hepatic diseases, and hepatocytes apoptosis contributes to the development of liver fibrosis following various causes. However, the mechanism of the Fas/FasL signaling and hepatocytes apoptosis in liver fibrogenesis remains unclear. The Fas/FasL signaling and hepatocytes apoptosis in liver samples from both human sections and mouse models were investigated. NF-κBp65 wild-type mice (p65f/f), hepatocytes specific NF-κBp65 deletion mice (p65Δhepa), p53-upregulated modulator of apoptosis (PUMA) wild-type (PUMA-WT) and PUMA knockout (PUMA-KO) littermate models, and primary hepatic stellate cells (HSCs) were also used. The mechanism underlying Fas/FasL-regulated hepatocytes apoptosis to drive HSCs activation in fibrosis was further analyzed. We found Fas/FasL promoted PUMA-mediated hepatocytes apoptosis via regulating autophagy signaling and NF-κBp65 phosphorylation, while inhibition of autophagy or PUMA deficiency attenuated Fas/FasL-modulated hepatocytes apoptosis and liver fibrosis. Furthermore, NF-κBp65 in hepatocytes repressed PUMA-mediated hepatocytes apoptosis via regulating the Bcl-2 family, while NF-κBp65 deficiency in hepatocytes promoted PUMA-mediated hepatocytes apoptosis and enhanced apoptosis-linked inflammatory response, which contributed to the activation of HSCs and liver fibrogenesis. These results suggest that Fas/FasL contributes to NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to enhance liver fibrogenesis, and this network could be a potential therapeutic target for liver fibrosis.

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Out with the bad: Studying autophagy to fight infectious disease

Cited by 2 publications

References 10 publications

β‐Arrestin1 enhances liver fibrosis through autophagy‐mediated Snail signaling

β‐Arrestin1 enhances liver fibrosis through autophagy‐mediated Snail signaling

Fas/FasL mediates NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to drive liver fibrosis

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