Tubule-derived exosomes play a central role in fibroblast activation and kidney fibrosis

Liu, Xi; Miao, Jinhua; Wang, Cong; Zhou, Shi‐Ping; Chen, Shuangqin; Ren, Qian; Xue, Hong; Wang, Yongping; Hou, Fan Fan; Zhou, Lili; Liu, Youhua

doi:10.1016/j.kint.2019.11.026

Cited by 93 publications

(83 citation statements)

References 47 publications

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“…Tubule-derived exosomes may play an essential role in driving renal fibroblast activation and fibrogenesis. Borges et al, 2013;Guan et al, 2020 5/6 nephrectomy) (Liu et al, 2020). Stimulation of cultured renal epithelial cells with TGF-β1 also increased exosome production, and the exosome purified from these cells are able to induce renal interstitial fibroblast activation (Liu et al, 2020).…”

Section: Evs Mediated Cell-cell Communication During Emtmentioning

confidence: 99%

“…Vesicles incorporate molecules from their origin cells containing proteins, nucleic acids and lipids ( Rigalli et al, 2020 ). A recent study demonstrated that exosomes are produced in renal proximal tubular epithelium following various fibrotic injury (UUO, ischemia/reperfusion or 5/6 nephrectomy) ( Liu et al, 2020 ). Stimulation of cultured renal epithelial cells with TGF-β1 also increased exosome production, and the exosome purified from these cells are able to induce renal interstitial fibroblast activation ( Liu et al, 2020 ).…”

Section: Epigenetic Regulation Of Pemt In the Kidneymentioning

confidence: 99%

“…A recent study demonstrated that exosomes are produced in renal proximal tubular epithelium following various fibrotic injury (UUO, ischemia/reperfusion or 5/6 nephrectomy) ( Liu et al, 2020 ). Stimulation of cultured renal epithelial cells with TGF-β1 also increased exosome production, and the exosome purified from these cells are able to induce renal interstitial fibroblast activation ( Liu et al, 2020 ). Conversely, pharmacologic inhibition of exosome secretion or depletion of exosome from the conditioned media blocked the ability of TGF-β1 stimulated renal epithelial cells to induce renal fibroblast activation; injection of tubular cell-derived exosomes also enhanced kidney injury and fibrosis ( Liu et al, 2020 ).…”

Section: Epigenetic Regulation Of Pemt In the Kidneymentioning

confidence: 99%

“…Stimulation of cultured renal epithelial cells with TGF-β1 also increased exosome production, and the exosome purified from these cells are able to induce renal interstitial fibroblast activation ( Liu et al, 2020 ). Conversely, pharmacologic inhibition of exosome secretion or depletion of exosome from the conditioned media blocked the ability of TGF-β1 stimulated renal epithelial cells to induce renal fibroblast activation; injection of tubular cell-derived exosomes also enhanced kidney injury and fibrosis ( Liu et al, 2020 ). Given that TGF-β1 is a potent inducer of partial EMT and all three fibrotic injuries cited by Liu et al (2020) can induce EMT, these results suggest that tubule-derived exosomes play an essential role in driving renal fibroblast activation and fibrogenesis.…”

Section: Epigenetic Regulation Of Pemt In the Kidneymentioning

confidence: 99%

“…Conversely, pharmacologic inhibition of exosome secretion or depletion of exosome from the conditioned media blocked the ability of TGF-β1 stimulated renal epithelial cells to induce renal fibroblast activation; injection of tubular cell-derived exosomes also enhanced kidney injury and fibrosis ( Liu et al, 2020 ). Given that TGF-β1 is a potent inducer of partial EMT and all three fibrotic injuries cited by Liu et al (2020) can induce EMT, these results suggest that tubule-derived exosomes play an essential role in driving renal fibroblast activation and fibrogenesis. Since tubule-derived exosomes contain numerous miRNAs and growth factors that are beneficial to renal recovery and repair, TECs may also employ exosomes to regulate renal reparative responses ( Borges et al, 2013 ; Guan et al, 2020 ).…”

Section: Epigenetic Regulation Of Pemt In the Kidneymentioning

confidence: 99%

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New Insights Into the Role and Mechanism of Partial Epithelial-Mesenchymal Transition in Kidney Fibrosis

2020

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Epithelial-mesenchymal transition (EMT) is described as the process in which injured renal tubular epithelial cells undergo a phenotype change, acquiring mesenchymal characteristics and morphing into fibroblasts. Initially, it was widely thought of as a critical mechanism of fibrogenesis underlying chronic kidney disease. However, evidence that renal tubular epithelial cells can cross the basement membrane and become fibroblasts in the renal interstitium is rare, leading to debate about the existence of EMT. Recent research has demonstrated that after injury, renal tubular epithelial cells acquire mesenchymal characteristics and the ability to produce a variety of profibrotic factors and cytokines, but remain attached to the basement membrane. On this basis, a new concept of "partial epithelial-mesenchymal transition (pEMT)" was proposed to explain the contribution of renal epithelial cells to renal fibrogenesis. In this review, we discuss the concept of pEMT and the most recent findings related to this process, including cell cycle arrest, metabolic alternation of epithelial cells, infiltration of immune cells, epigenetic regulation as well as the novel signaling pathways that mediate this disturbed epithelial-mesenchymal communication. A deeper understanding of the role and the mechanism of pEMT may help in developing novel therapies to prevent and halt fibrosis in kidney disease.

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Section: Evs Mediated Cell-cell Communication During Emtmentioning

confidence: 99%

Section: Epigenetic Regulation Of Pemt In the Kidneymentioning

confidence: 99%

Section: Epigenetic Regulation Of Pemt In the Kidneymentioning

confidence: 99%

Section: Epigenetic Regulation Of Pemt In the Kidneymentioning

confidence: 99%

Section: Epigenetic Regulation Of Pemt In the Kidneymentioning

confidence: 99%

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New Insights Into the Role and Mechanism of Partial Epithelial-Mesenchymal Transition in Kidney Fibrosis

2020

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Reversing Acute Kidney Injury through Coordinated Interplay of Anti‐Inflammation and Iron Supplementation

et al. 2023

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Acute kidney injury (AKI) induced by ischemia reperfusion isclosely related to mitochondrial dysfunction. Nicotinamide adenine dinucleotide (NAD + ) can enhance the mitochondrial function and restrain the following inflammation, but it is hardly delivered and lacks renal targeting ability. To address these problems, herein, an ultrasmall Fe 3 O 4 nanoparticle is used as a carrier to deliver nicotinamide mononucleotide (NMN), a precursor of NAD + . An outstanding sophistication of the current design is that once NMN is attached on the surface of Fe 3 O 4 nanoparticles through its phosphate group, the remaining part is structurally highly similar to nicotinamide riboside, which provides an opportunity to deliver the NAD + precursor into renal cells through nicotinamide riboside kinase 1 on the cell membrane. It is demonstrated that NMN-loaded Fe 3 O 4 nanoparticles can effectively reverse AKI induced by ischemia reperfusion. In-depth studies indicate that a well-timed iron replenishment following anti-inflammation treatment plays a determined role in recovering AKI, which distinguishes the current study from previous strategies centering on anti-ROS (reactive oxygen species), anti-inflammation, or even iron elimination.

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Mitocytosis Mediated by an Enzyme‐Activable Mitochondrion‐Disturbing Polymer‐Drug Conjugate Enhances Active Penetration in Glioblastoma Therapy

Xiang,

Wang,

Yang

et al. 2024

Advanced Materials

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The application of nanomedicines for glioblastoma (GBM) therapy is hampered by the blood‐brain barrier (BBB) and the dense glioblastoma tissue. To achieve efficient BBB crossing and deep GBM penetration, we demonstrated a strategy of active transcellular transport of a mitochondrion‐disturbing nanomedicine, GBEPPT, in the GBM tissue through mitocytosis. GBEPPT was computer‐aided designed and prepared by self‐assembling a conjugate of an amphiphilic block polymer and a drug podophyllotoxin (PPT). When GBEPPT was delivered to the tumor site, overexpressed γ‐glutamyl transpeptidase (GGT) on the brain‐blood endothelial cell or the GBM cell triggered enzymatic hydrolysis of γ‐glutamylamide on GBEPPT to reverse its charge. Positively‐charged GBEPPT rapidly entered into the cell and targeted the mitochondria. These GBEPPT disturbed the homeostasis of mitochondria, inducing mitocytosis‐mediated extracellular transport of GBEPPT to the neighboring cells via mitosomes. This intracellular‐to‐intercellular delivery cycle allowed GBEPPT to penetrate deeply into the GBM parenchyma, and exert sustainable action of PPT released from GBEPPT on the tumor cells along its penetration path at the tumor site, thus improving the anti‐GBM effect. The process of mitocytosis mediated by the mitochondrion‐disturbing nanomedicine may offer great potential in enhancing drug penetration through malignant tissues, especially poorly permeable solid tumors.This article is protected by copyright. All rights reserved

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Tubule-derived exosomes play a central role in fibroblast activation and kidney fibrosis

Cited by 93 publications

References 47 publications

New Insights Into the Role and Mechanism of Partial Epithelial-Mesenchymal Transition in Kidney Fibrosis

New Insights Into the Role and Mechanism of Partial Epithelial-Mesenchymal Transition in Kidney Fibrosis

Reversing Acute Kidney Injury through Coordinated Interplay of Anti‐Inflammation and Iron Supplementation

Mitocytosis Mediated by an Enzyme‐Activable Mitochondrion‐Disturbing Polymer‐Drug Conjugate Enhances Active Penetration in Glioblastoma Therapy

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