Mannan-Binding Lectin via Interaction With Cell Surface Calreticulin Promotes Senescence of Activated Hepatic Stellate Cells to Limit Liver Fibrosis Progression

Luo, Jialiang; Li, Lei; Chang, Bo Yoon; Zhu, Zhengyumeng; Deng, Fan; Hu, Mengyao; Yu, Yu; Xiao, Lü; Chen, Zhengliang; Zuo, Daming; Zhou, Jia

doi:10.1016/j.jcmgh.2022.03.011

Cited by 16 publications

(11 citation statements)

References 65 publications

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“…Cell lysis was centrifuged at 12,000 g for 10 min at 4 °C and the cell supernatants were collected. The following procedures were performed as previously described [ 18 ]. For immunoprecipitation, cell lysate was incubated with 1 µg of anti-TGF-β receptor I or II antibody and protein A/G agarose (Santa Cruz Biotechnology, USA) at 4 °C overnight, respectively.…”

Section: Methodsmentioning

confidence: 99%

FUT1-mediated terminal fucosylation acts as a new target to attenuate renal fibrosis

Luo

Mao

Zhu

et al. 2023

Mol Med

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Backgrounds Renal fibrosis is a common pathologic process of most chronic kidney diseases (CKDs), becoming one of the major public health problems worldwide. Terminal fucosylation plays an important role in physiological homeostasis and pathological development. The present study aimed to explore the role of terminal fucosylation during kidney fibrogenesis and propose a possible anti-fibrosis treatment via suppressing aberrant terminal fucosylation. Methods We investigated the expression level of fucosyltransferase1 (FUT1) in CKD patients by using public database. Then, we further confirmed the level of terminal fucosylation by UEA-I staining and FUT1 expression in unilateral ureteral obstruction (UUO)-induced renal fibrosis mice. Immunostaining, qPCR, western blotting and wound healing assay were applied to reveal the effect of FUT1 overexpression in human kidney proximal tubular epithelial cell (HK-2). What’s more, we applied terminal fucosylation inhibitor, 2-Deoxy-D-galactose (2-D-gal), to determine whether suppressing terminal fucosylation ameliorates renal fibrosis progression in vitro and in vivo. Results Here, we found that the expression of FUT1 significantly increased during renal fibrosis. In vitro experiments showed upregulation of epithelial-mesenchymal transition (EMT) after over-expression of FUT1 in HK-2. Furthermore, in vivo and in vitro experiments indicated that suppression of terminal fucosylation, especially on TGF-βR I and II, could alleviate fibrogenesis via inhibiting transforming growth factor-β (TGF-β)/Smad signaling. Conclusions The development of kidney fibrosis is attributed to FUT1-mediated terminal fucosylation, shedding light on the inhibition of terminal fucosylation as a potential therapeutic treatment against renal fibrosis.

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Section: Methodsmentioning

confidence: 99%

FUT1-mediated terminal fucosylation acts as a new target to attenuate renal fibrosis

Luo

Mao

Zhu

et al. 2023

Mol Med

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“…Preclinical studies of senolytic therapies for liver diseases have shown promising results. The classic senolytic cocktail of dasatinib plus quercetin (D + Q) reduced overall hepatic steatosis, thus alleviating aging-related NAFLD 119 and CCl 4 -induced liver fibrosis 157 in mice. Fisetin has also been shown to improve APAP-induced hepatotoxicity by promoting autophagy and inhibiting inflammasome activation 158 .…”

Section: Promising Therapeutics Targeting Agingmentioning

confidence: 99%

The Roles of Myeloid Cells in Aging-related Liver Diseases

Yao¹,

Li²,

Wang³

2023

Int. J. Biol. Sci.

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Aging is a necessary process of life associated with various mechanisms, such as genomic instability, loss of proteostasis, deregulated nutrient sensing, and cellular senescence, causing progressive dysregulation of the microenvironment, organ homeostasis and biological functions. The hepatic microenvironment is essential for maintaining liver homeostasis, in which hepatocytes, sinusoidal endothelial cells, stellate cells and immune cells are closely associated with the development of aging-related liver diseases. There is increasing evidence that immunocytes, especially myeloid cells, are involved in aging-related liver diseases such as alcoholic liver disease, nonalcoholic liver disease, liver fibrosis or cirrhosis and liver cancer, becoming promising treatment targets of these diseases. This review summarizes the phenotypic and functional alterations associated with aging liver and myeloid cells, as well as the roles of myeloid cells in the progression of aging-related liver diseases.

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“…MBL was found to directly interact with calcium reticulin related with low-density lipoprotein receptor-contacted protein 1 on HSCs cells surface, additional promoting HSCs decrepitude through upregulation of mammalian rapamycin/p53/p21 signaling targets. Thus, activated HSCs with a decrepit phenotype may support manage or reverse LF though cutting down ECM levels, thereby re-establishing a quiescent environment [95] . Autophagy is a self-degrading process.…”

Section: Notch Signaling Pathway Acts On Hscs Through Other Signaling...mentioning

confidence: 99%

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

Zheng

Yang

Luo

et al. 2022

Preprint

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Liver fibrosis (LF) is a trauma repair process carried out by the liver in response to various acute and chronic liver injuries, featured by excessive proliferation as well as abnormal dismissal of extracellular matrix as the main pathological features, and its continuous development will deteriorate into cirrhosis, liver cancer as well as other illnesses. The occurrence of LF is closely related to Hepatic stellate cells (HSCs) stimulation, and intervention in HSCs proliferation is expected to reverse LF. Plant-based small molecule drugs have anti-LF effects, and their mechanisms of action are related to anti-inflammation, anti-oxidative stress, as well as inhibition of abnormal accumulation of extracellular matrix. Consequently, new agents for HSCs will be required to furnish a possible curative response. Small-molecule natural products might be attractive for LF therapy. That is because they not only have the effect against HSCs, but also have excellent qualities such as low toxic side effects and easy availability from the perspective of safety and cost. In this review, we provide an updated review of the signal transduction pathways involved in HSCs and small-molecule natural products targeting HSCs reported in the past 3 years at home and abroad, with the aim of providing new ideas for the development of plant-based small molecule drugs targeting HSCs to reverse LF.

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Mannan-Binding Lectin via Interaction With Cell Surface Calreticulin Promotes Senescence of Activated Hepatic Stellate Cells to Limit Liver Fibrosis Progression

Cited by 16 publications

References 65 publications

FUT1-mediated terminal fucosylation acts as a new target to attenuate renal fibrosis

FUT1-mediated terminal fucosylation acts as a new target to attenuate renal fibrosis

The Roles of Myeloid Cells in Aging-related Liver Diseases

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

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