Fibrosis‐on‐Chip: A Guide to Recapitulate the Essential Features of Fibrotic Disease DOI Creative Commons
Emma M. Streutker, Utku Devamoglu, Madelon C Vonk

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(21)

Published: March 27, 2024

Fibrosis, which is primarily marked by excessive extracellular matrix (ECM) deposition, a pathophysiological process associated with many disorders, ultimately leads to organ dysfunction and poor patient outcomes. Despite the high prevalence of fibrosis, currently there exist few therapeutic options, importantly, paucity in vitro models accurately study fibrosis. This review discusses multifaceted nature fibrosis from viewpoint developing organ-on-chip (OoC) disease models, focusing on five key features: ECM component, inflammation, mechanical cues, hypoxia, vascularization. The potential OoC technology explored for better modeling these features context studying fibrotic diseases interplay between various emphasized. paper reviews how organ-specific are modeled platforms, elements included existing avenues novel research directions highlighted. Finally, this concludes perspective address current gap respect inclusion multiple yield more sophisticated relevant an format.

Language: Английский

si-Tgfbr1-loading liposomes inhibit shoulder capsule fibrosis via mimicking the protective function of exosomes from patients with adhesive capsulitis DOI Creative Commons
Yaying Sun, Zhiwen Luo, Yisheng Chen

et al.

Biomaterials Research, Journal Year: 2022, Volume and Issue: 26(1)

Published: Aug. 19, 2022

Adhesive capsulitis is a common shoulder disorder inducing joint capsule fibrosis and pain. When combined with rotator cuff tear (RCT), treatments can be more complex. Currently, targeted therapy lacking. Since adhesive reported to related circulating materials, we analyzed the contents biology of exosomes from RCT patients without capsulitis, in an attempt developing targeting treatment. Samples consecutive cohort for surgery were collected. Circulating exosomal miRNAs sequencing used detect differentially expressed capsulitis. For experiments vitro, Brdu staining, CCK-8 assay, wound healing test, collagen contraction real-time quantitative polymerase chain reaction, western blot conducted. Histological immunofluorescent biomechanical analysis applied mouse model stiffness. The characteristics liposomes loaded siRNA measured via dynamic light scattering or electron microscopy. showed that, compared miR-142 was significantly up-regulated (Exo-S). Both Exo-S could inhibit fibrogenesis, anti-fibrotic effect relied on miR-142. target proven transforming growth factor β receptor 1 (Tgfbr1). Then, developed si-Tgfbr1. si-Tgfbr1-loading exhibited promising therapeutic against stiffness no evidence toxicity. This study are protective have potential. contained miR-142, which targets Tgfbr1. By mimicking this biological function, si-Tgfbr1 mitigate pre-clinically.

Language: Английский

Citations

38
Epithelial–mesenchymal plasticity in kidney fibrosis DOI

Sudarat Hadpech,

Visith Thongboonkerd

genesis, Journal Year: 2023, Volume and Issue: 62(1)

Published: June 22, 2023

Summary Epithelial–mesenchymal transition (EMT) is an important biological process contributing to kidney fibrosis and chronic disease. This characterized by decreased epithelial phenotypes/markers increased mesenchymal phenotypes/markers. Tubular cells (TECs) are commonly susceptible EMT various stimuli, for example, transforming growth factor‐β (TGF‐β), cellular communication network factor 2, angiotensin‐II, fibroblast factor‐2, oncostatin M, matrix metalloproteinase‐2, tissue plasminogen activator (t‐PA), plasmin, interleukin‐1β, reactive oxygen species. Similarly, glomerular podocytes can undergo via these stimuli high glucose condition in diabetic of TECs leads tubulointerstitial glomerulosclerosis, respectively. Signaling pathways involved EMT‐mediated diverse complex. TGF‐β1/Smad Wnt/β‐catenin the major venues triggering podocytes. These two thus serve as therapeutic targets against fibrosis. To date, a number inhibitors have been identified characterized. As expected, majority affect pathways. In addition fibrosis, EMT‐targeted antifibrotic expected be effective treatment other organs/tissues.

Language: Английский

Citations

29
The role of epithelial cells in fibrosis: Mechanisms and treatment DOI Creative Commons

Liuyi Luo,

Wei Zhang,

Siyao You

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 202, P. 107144 - 107144

Published: March 13, 2024

Fibrosis is a pathological process that affects multiple organs and considered one of the major causes morbidity mortality in diseases, resulting an enormous disease burden. Current studies have focused on fibroblasts myofibroblasts, which directly lead to imbalance generation degradation extracellular matrix (ECM). In recent years, increasing number role epithelial cells fibrosis. some cases, are first exposed external physicochemical stimuli may drive collagen accumulation mesenchyme. other source stimulation mainly immune cytokines, similarly altered process. this review, we will focus dynamic alterations involved after injury during fibrogenesis, discuss association among them, summarize therapies targeting changed cells. Especially, mesenchymal transition (EMT) key central step, closely linked biological behaviors. Meanwhile, think disruption barrier, cell death basal stem populations stemness fibrosis not appreciated. We believe targeted can prevent progress fibrosis, but reverse it. The provide wonderful preventive delaying action.

Language: Английский

Citations

9
Pedunculoside inhibits epithelial-mesenchymal transition and overcomes Gefitinib-resistant non-small cell lung cancer through regulating MAPK and Nrf2 pathways DOI Creative Commons

Qiumei Fan,

Xiaowei Liang, Zhipeng Xu

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 116, P. 154884 - 154884

Published: May 16, 2023

Lung cancer is the primary cause of cancer-related mortality worldwide owing to its strong metastatic ability. EGFR-TKI (Gefitinib) has demonstrated efficacy in lung therapy, but most patients ultimately develop resistance Gefitinib, leading a poor prognosis. Pedunculoside (PE), triterpene saponin extracted from Ilex rotunda Thunb., shown anti-inflammatory, lipid-lowering and anti-tumor effects. Nevertheless, therapeutic effect potential mechanisms PE on NSCLC treatment are unclear.To investigate inhibitory prospective metastases Gefitinib-resistant NSCLC.In vitro, A549/GR cells were established by Gefitinib persistent induction A549 with low dose shock high dose. The cell migratory ability was measured using wound healing Transwell assays. Additionally, EMT-related Markers or ROS production assessed RT-qPCR, immunofluorescence, Western blotting, flow cytometry assays TGF-β1-induced cells. In vivo, B16-F10 intravenously injected into mice, tumor determined hematoxylin-eosin staining, Caliper IVIS Lumina, DCFH2-DA western blotting assays.PE reversed EMT downregulating protein expression through MAPK Nrf2 pathways, decreasing production, inhibiting migration invasion Moreover, enabled retrieve sensitivity mitigate biological characteristics EMT. also significantly inhibited metastasis mice reversing proteins expression, pathways.Collectively, this research presents novel finding that can reverse improve subsequently suppressing model. Our findings indicate agent for improving NSCLC.

Language: Английский

Citations

19
Modelling and targeting mechanical forces in organ fibrosis DOI
Shamik Mascharak, Jason L. Guo, Michelle Griffin

et al.

Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: 2(4), P. 305 - 323

Published: Jan. 18, 2024

Language: Английский

Citations

7
Kidney Fibrosis and Matrix Metalloproteinases (MMPs) DOI Creative Commons
Antonella La Russa, Raffaele Serra,

Teresa Faga

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(5)

Published: May 16, 2024

Chronic kidney disease (CKD) is a disorder that causes changes in both the structure and function of kidneys, causing complications such as hypertension, edema, oliguria. Renal fibrosis also common pathological feature CKD. Matrix metalloproteinases (MMPs) are endopeptidases degrade extracellular matrix (ECM) proteins. The proteinase domain consists zinc ion active site, which contributes to its stabilization with another three calcium structural ions. Many cellular processes controlled by MMPs, cell–cell interactions various signaling pathways, while they involved degrading substrates on cell surfaces. Tissue inhibitors (TIMPs) key regulators metalloproteinases, regulating turnover, regulation, progression apoptosis tissue. MMPs play role renal fibrosis, tubular epithelial–mesenchymal transition (TEM), activation resident fibroblasts, endothelial–mesenchymal (EndoMT), pericyte–myofibroblast transdifferentiation. This review aims show mechanisms through contribute paying particular attention MMP-9 transition.

Language: Английский

Citations

7
Role of cellular senescence in the pathogenesis of systemic sclerosis DOI
Pei‐Suen Tsou, Bo Shi, John Varga

et al.

Current Opinion in Rheumatology, Journal Year: 2022, Volume and Issue: 34(6), P. 343 - 350

Published: Aug. 16, 2022

Purpose of review Systemic sclerosis (SSc) is a chronic rheumatic disease that characterized by immune activation, vasculopathy and fibrosis the skin internal organs. It has been proposed premature onset ageing pathways associated senescent changes in cells contribute to clinical pathological features SSc. The aim this critically recent insights into involvement cellular senescence Recent findings Cellular plays critical role SSc pathogenesis, particularly involving endothelial fibroblasts. Immunosenescence could also pathogenesis direct alteration functions or indirect promotion defective surveillance. Molecular studies have shed some light on how contributes fibrosis. planned proof-of-concept trials using senotherapeutics showed promising results fibrotic diseases, including Summary There increasing evidence implicating mechanisms underlying SSc, its potential merit further investigation. Emerging drugs targeting senescence-related might be therapeutic options for

Language: Английский

Citations

23
The Gut-Peritoneum Axis in Peritoneal Dialysis and Peritoneal Fibrosis DOI Creative Commons
N. Stepanova

Kidney Medicine, Journal Year: 2023, Volume and Issue: 5(6), P. 100645 - 100645

Published: April 20, 2023

Language: Английский

Citations

13
Copper Exposure Induces Epithelial-Mesenchymal Transition-Related Fibrotic Change via Autophagy and Increase Risk of Lung Fibrosis in Human DOI Creative Commons
Hung‐Yi Chiou, Chih‐Wen Wang, Szu‐Chia Chen

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 532 - 532

Published: Feb. 20, 2023

Copper is an essential trace element involved in several vital biological processes of the human body. However, excess exposure to copper caused by occupational hazards and environmental contamination, such as food, water, air, damages health. In this study, vitro cell culture model epidemiologic studies were conducted evaluate effect on lung fibrosis. vitro, treatment CuSO4 epithelial cells at 100 μM consistently decreases viability alveolar type (A549) bronchial (HBE) cells. promotes epithelial-mesenchymal transition (EMT) shown increased migration EMT marker fibrotic gene expressions. Besides, induced autophagy, with LC3, PINK, decreased p62 expression. Inhibition ROS N-acetylcysteine reversed CuSO4-induced PINK1, Snail autophagy chloroquine reverses changes. Nature flavonoids, especially kaempferol, fustin, inhibit Copper-induced EMT. humans, a unit increase urinary concentration was significantly associated risk changes (odds ratio [OR] = 1.17, 95% confidence interval [CI] 1.01–1.36, p 0.038). These results indicated that factor for fibrosis through activation ROS-autophagy-EMT pathway, which can be flavonoids.

Language: Английский

Citations

12
Interactions between circRNAs and miR-141 in Cancer: From Pathogenesis to Diagnosis and Therapy DOI Open Access
Małgorzata Guz, Witold Jeleniewicz, Marek Cybulski

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11861 - 11861

Published: July 24, 2023

The function of non-coding RNAs (ncRNAs) in the pathogenesis and development cancer is indisputable. Molecular mechanisms underlying carcinogenesis involve aberrant expression ncRNAs, including circular (circRNAs), microRNAs (miRNAs). CircRNAs are a class single-stranded, covalently closed responsible for maintaining cellular homeostasis through their diverse functions. As part competing endogenous RNA (ceRNAs) network, they play central role regulation accessibility miRNAs to mRNA targets. interplay between these molecular players based on primary circRNAs that act as sponges, circRNA/miRNA imbalance plays different pathologies cancer. Herein, we present latest state knowledge about interactions miR-141, well-known member miR-200 family, malignant transformation, with emphasis biological circRNA/miR-141/mRNA networks future target novel anti-cancer therapies.

Language: Английский

Citations

11