Core fucosylation involvement in the paracrine regulation of proteinuria-induced renal interstitial fibrosis evaluated with the use of a microfluidic chip

Liu, Anqi; Wang, Xiaolang; Hu, Xuemei; Deng, Yiyao; Xu, Wen; Lin, Baiquan; Zhou, Ming; Wang, Weidong; Luo, Yong; Deng, Jiu; Tang, Qingzhu; Du, Xiangning; Qin, Biaojie; Song, Huiyi; Lin, Hongli

doi:10.1016/j.actbio.2022.02.020

Cited by 11 publications

(5 citation statements)

References 60 publications

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“…Although integration of renal vasculature may not be considered as a MOC setup, the combination of either the proximal tubule or glomerulus with endothelium is reported in 31 publications ( Table S2 ). The addition of vasculature allows for a more physiological nephron construction while mimicking the renal interstitial micro-environment ( Zhou et al, 2016 ; Chapron et al, 2020 ; Liu et al, 2022 ), allowing assessment of tubular drug secretion ( Chapron et al, 2020 ; Imaoka et al, 2021 ) and modeling diseases involving renal peritubular microvessels ( Liu et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

A systematic review of kidney-on-a-chip-based models to study human renal (patho-)physiology

Nguyen

Gkouzioti

Maaß

et al. 2023

Disease Models &Amp; Mechanisms

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As kidney diseases affect ∼10% of the world population, understanding the underlying mechanisms and developing therapeutic interventions are of high importance. Although animal models have enhanced knowledge of disease mechanisms, human (patho-)physiology may not be adequately represented in animals. Developments in microfluidics and renal cell biology have enabled the development of dynamic models to study renal (patho-)physiology in vitro. Allowing inclusion of human cells and combining different organ models, such as kidney-on-a-chip (KoC) models, enable the refinement and reduction of animal experiments. We systematically reviewed the methodological quality, applicability and effectiveness of kidney-based (multi-)organ-on-a-chip models, and describe the state-of-the-art, strengths and limitations, and opportunities regarding basic research and implementation of these models. We conclude that KoC models have evolved to complex models capable of mimicking systemic (patho-)physiological processes. Commercial chips and human induced pluripotent stem cells and organoids are important for KoC models to study disease mechanisms and assess drug effects, even in a personalized manner. This contributes to the Reduction, Refinement and Replacement of animal models for kidney research. A lack of reporting of intra- and inter-laboratory reproducibility and translational capacity currently hampers implementation of these models.

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Section: Resultsmentioning

confidence: 99%

A systematic review of kidney-on-a-chip-based models to study human renal (patho-)physiology

Nguyen

Gkouzioti

Maaß

et al. 2023

Disease Models &Amp; Mechanisms

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show abstract

“…Increasing core fucosylation activates downstream signaling pathways, such as the Smad2/3 and ERK pathways. Most of these studies targeted animal models with peritoneal fibrosis, renal interstitial fibrosis, or pulmonary fibrosis and found that inhibiting FUT8 expression inhibited disease progression [68][69][70][71][72][73]. Limited studies have focused on the role of FUT8 in the cardiovascular system, but only one study has demonstrated that FUT8 regulates the TGFβ/Smad2/3 signaling pathway in the aortic smooth muscle of a uremia rat model by influencing core fucosylation of TGF-βR II and ALK5, resulting in vascular calcification [74].…”

Section: Discussionmentioning

confidence: 99%

FUT8-Mediated Core Fucosylation Promotes the Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

Zhang¹,

Lin²,

Zeng³

et al. 2023

Aging and disease

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Pulmonary arterial hypertension (PAH) is a progressive cardiopulmonary disease with unclearunderlying molecular mechanisms and limited therapeutic options. This study aimed to explore the role of core fucosylation and the only glycosyltransferase FUT8 in PAH. We observed increased core fucosylation in a monocrotaline (MCT)-induced PAH rat model and isolated rat pulmonary artery smooth muscle cells (PASMCs) treated with platelet-derived growth factor-BB (PDGF-BB). We found that 2-fluorofucose (2FF), a drug used to inhibit core fucosylation, improved hemodynamics and pulmonary vascular remodeling in MCT-induced PAH rats. In vitro, 2FF effectively restrains the proliferation, migration, and phenotypic switching of PASMCs and promotes apoptosis. Compared with controls, serum FUT8 concentration in PAH patients and MCT-induced rats was significantly elevated. FUT8 expression appeared increased in the lung tissues of PAH rats, and the colocalization of FUT8 with α-SMA was also observed. SiRNA was used to knockdown FUT8 in PASMCs (siFUT8). After effectively silencing FUT8 expression, phenotypic changes induced in PASMCs by PDGF-BB stimulation were alleviated. FUT8 activated the AKT pathway, while the admission of AKT activator SC79 could partially counteract the negative effect of siFUT8 on the proliferation, apoptotic resistance, and phenotypic switching of PASMCs, which may be involved in the core fucosylation of vascular endothelial growth factor receptor (VEGFR). Our research confirmed the critical role of FUT8 and its mediated core fucosylation in pulmonary vascular remodeling in PAH, providing a potential novel therapeutic target for PAH.

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“…Liu et al. [ 110 ] developed a renal tubule-vascular chip to create a proteinuria model. The results suggested that it was involved in the crosstalk between renal tubules and peritubular microvessels in renal interstitial fibrosis induced by proteinuria, and inhibition of receptor fucosyltransferase 8 could reverse the injury of peritubular microvessels and renal interstitial fibrosis.…”

Section: Microfluidic Chips Of Urinary System Diseases With Microenvi...mentioning

confidence: 99%

Application of microfluidic chips in the simulation of the urinary system microenvironment

Chao-zhen¹,

Gu²,

Yuan³

et al. 2023

Materials Today Bio

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Core fucosylation involvement in the paracrine regulation of proteinuria-induced renal interstitial fibrosis evaluated with the use of a microfluidic chip

Cited by 11 publications

References 60 publications

A systematic review of kidney-on-a-chip-based models to study human renal (patho-)physiology

A systematic review of kidney-on-a-chip-based models to study human renal (patho-)physiology

FUT8-Mediated Core Fucosylation Promotes the Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

Application of microfluidic chips in the simulation of the urinary system microenvironment

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