Shear stress–induced cellular senescence blunts liver regeneration through Notch–sirtuin 1–P21/P16 axis

Duan, Jialin; Ruan, Bai; Song, Ping; Fang, Zhiqiang; Yue, Zhen-Sheng; Liu, Jingjing; Dou, Guo‐Rui; Han, Hua; Wang, Lin

doi:10.1002/hep.32209

Cited by 69 publications

(46 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SIRT1 (Sir2) is a class III histone deacetylase that is deeply involved in an extensive range of biological events, containing immune response, metabolism, and aging. Numerous studies demonstrated that SIRT1 showed deficiency in various organs such as the liver, heart, lung, and kidney in the course of senescence ( D’Onofrio et al, 2018 ; Duan et al, 2021 ; Ryu et al, 2019 ). SIRT1 also functions as a cytoplasmic energy sensor of NAD+/NADH ratio to maintain mitochondrial metabolism homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Arbutin Protects Retinal Pigment Epithelium Against Oxidative Stress by Modulating SIRT1/FOXO3a/PGC-1α/β Pathway

Tang

Kuang

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

Age-related macular degeneration (AMD), which is the leading cause of blindness among the elderly in western societies, is majorly accompanied by retinal pigment epithelium (RPE) degeneration. Because of the irreversible RPE cell loss among oxidative stress, it is crucial to search for available drugs for atrophic (dry) AMD. RNA-Seq analysis revealed that genes related to aging and mitochondrial health were differentially expressed under Arbutin treatment, whereas compared to oxidative injury, our study demonstrated that Arbutin substantially abrogated oxidative stress-induced cell senescence and apoptosis linked to intracellular antioxidant enzyme system homeostasis maintenance, restored mitochondrial membrane potential (MMP), and reduced the SA-β-GAL accumulation in RPE. Furthermore, Arbutin alleviated oxidative stress-mediated cell apoptosis and senescence via activation of SIRT1, as evidenced by the increase of the downstream FoxO3a and PGC-1α/β that are related to mitochondrial biogenesis, and the suppression of NF-κB p65 inflammasome, whereas rehabilitation of oxidative stress by SIRT1 inhibitor attenuated the protective effect of Arbutin. In conclusion, we validated the results in an in vivo model constructed by NAIO3-injured mice. OCT and HE staining showed that Arbutin sustained retinal integrity in the case of oxidative damage in vivo, and the disorder of RPE cytochrome was alleviated through fundus observation. In summary, our findings identified that oxidative stress-induced mitochondrial malfunction and the subsequent senescence acceleration in RPE cells, whereas Arbutin inhibited TBHP-induced RPE degeneration via regulating the SIRT1/Foxo3a/PGC-1α/β signaling pathway. These findings suggested that Arbutin is a new agent with potential applications in the development of AMD diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Arbutin Protects Retinal Pigment Epithelium Against Oxidative Stress by Modulating SIRT1/FOXO3a/PGC-1α/β Pathway

Tang

Kuang

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…Furthermore, blood flow changes induced by PHx alter the remodeling of sinusoids affecting shear stressinduced eNOS, accounting for senescent LSECs via Notch activation, but Sirtuin 1 inhibition was able to promote liver regeneration by abolishing Notch-induced senescence (Duan et al 2022). The latter is the first study demonstrating that LSEC senescence is triggered by endothelial Notch activation, with Sirtuin 1 as a direct target of Notch (Duan et al 2022).…”

Section: R76 F Bellanti and Othersmentioning

confidence: 91%

“…This redox-sensitive mechanism can be pharmacologically modulated to accelerate the process of liver regeneration, as suggested by studies using prolactin-induced HIF-1α-VEGF axis or prolyl hydrolase inhibitors (Olazabal et al 2009, Schadde et al 2017. Furthermore, blood flow changes induced by PHx alter the remodeling of sinusoids affecting shear stressinduced eNOS, accounting for senescent LSECs via Notch activation, but Sirtuin 1 inhibition was able to promote liver regeneration by abolishing Notch-induced senescence (Duan et al 2022). The latter is the first study demonstrating that LSEC senescence is triggered by endothelial Notch activation, with Sirtuin 1 as a direct target of Notch (Duan et al 2022).…”

Section: R76 F Bellanti and Othersmentioning

confidence: 99%

Redox experimental medicine and liver regeneration

Bellanti

Vendemiale

Serviddio

2022

Redox Experimental Medicine

View full text Add to dashboard Cite

The liver is characterized by unique regenerative properties to restore its mass and function after a partial loss. Hepatic regeneration arises after resection or following acute and chronic injuries. Resection and acute liver damage normally induce a regenerative process characterized by phenotypic fidelity, in which each cell type promotes its own replication and replacement. This process fails in chronic liver damage, where trans-differentiation of parenchymal cells or activation of facultative progenitors occurs. Both liver resection and acute/chronic damages alter redox homeostasis, as a consequence of blood flow changes, hypoxia, metabolism modification, and activation of inflammatory response. Even though formerly described as ‘oxidative stress’, altered redox homeostasis leads to the fine regulation of several pathways involved in liver regeneration, including the proliferation of parenchymal cells, trans-differentiation, and activation of facultative progenitors. Several redox-dependent transcription factors and pathways implicated in the regenerative process of the liver were described, but pre-clinical experiments using different antioxidants were not fully conclusive. Even though accurate study designs to define appropriate dosages, treatment duration, and routes of administration are required, modulation of redox-dependent molecular pathways to enhance liver regeneration is even more intriguing. Preliminary studies focused on the identification of these targets will pave the way for viable therapies to be tested in clinical trials.

show abstract

“…Interestingly, patients with pre-eclampsia exhibit senescence and dysfunction of endothelial progenitor cells [91,92]. And SIRT1 protects endothelial cells from senescence by various pathways, such as p53, eNOs, Nrf2, FOXO3, and p21/p16, which can be regulated by several miRNA, including miR-217, miR-34a, miR-155, and miR-22 [93][94][95][96][97][98][99]. However, more evidence is needed to further verify the functions of SIRT1 in endothelial aging.…”

Section: Sirt1 Can Also Protect Endothelial Cells From Senescencementioning

confidence: 99%

SIRT1: A Novel Protective Molecule in Pre-eclampsia

Liu¹,

Wang²,

Pei³

et al. 2022

Int. J. Med. Sci.

View full text Add to dashboard Cite

Pre-eclampsia is a severe pregnant complication, mainly characterized by insufficient trophoblast invasion, impaired uterine spiral artery remodeling, placental hypoxia and ischemia, and endothelial dysfunction. However, the potential mechanisms of pre-eclampsia remain unclear. SIRT1 is a NAD+-dependent deacetylase, involving in multiple biological processes, including energy metabolism, oxidative stress, inflammatory response, and cellular autophagy. Several studies showed that SIRT1 might play a vital role in the pathogenesis of pre-eclampsia. In this review, we aim to integrate the latest research on SIRT1 and pre-eclampsia to explore the comprehensive mechanisms of SIRT1 in pre-eclampsia. More specifically, SIRT1 might affect placental development and trophoblast invasion through autophagy and senescence in pre-eclampsia, and SIRT1 protects vascular endothelial cells from oxidative stress, inflammatory response, autophagy, and senescence. Furthermore, SIRT1 deficiency mice showed typical pre-eclampsia-like performances, which can be reversed via direct SIRT1 supplement or SIRT1 agonist treatment. Additionally, resveratrol, a SIRT1 agonist, attenuates vascular endothelial injury and placental dysfunction, and exerts protective effect on decreasing blood pressure. In this review, we provide new insights into the development of pre-eclampsia, which can establish a theoretical basis for prevention and treatment for pre-eclampsia. Besides, we also propose questions that still need to be further addressed in order to elucidate the comprehensive molecular mechanisms of pre-eclampsia in the future.

show abstract

Shear stress–induced cellular senescence blunts liver regeneration through Notch–sirtuin 1–P21/P16 axis

Cited by 69 publications

References 42 publications

Arbutin Protects Retinal Pigment Epithelium Against Oxidative Stress by Modulating SIRT1/FOXO3a/PGC-1α/β Pathway

Arbutin Protects Retinal Pigment Epithelium Against Oxidative Stress by Modulating SIRT1/FOXO3a/PGC-1α/β Pathway

Redox experimental medicine and liver regeneration

SIRT1: A Novel Protective Molecule in Pre-eclampsia

Contact Info

Product

Resources

About