Cellular Senescence in the Kidney

Docherty, Marie-Helena; O’Sullivan, Eoin D.; Bonventre, Joseph V.; Ferenbach, David A.

doi:10.1681/asn.2018121251

Cited by 168 publications

(146 citation statements)

References 96 publications

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“…Increasing evidence indicates that the occurrence of EMT in renal tubular cells is associated with cellular senescence. Cellular senescence is mainly characterized by growth arrest and formation of a senescence-associated secretory phenotype that produces numerous profibrotic cytokines/growth factors, including TGF-β1 (Sosa Peña et al, 2018;Docherty et al, 2019). As mentioned, some growth factors and TGF-β1 not only induce renal fibroblast activation, but also stimulate the EMT response.…”

Section: Contribution Of Pemt To Renal Fibrosismentioning

confidence: 99%

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: Contribution Of Pemt To Renal Fibrosismentioning

confidence: 99%

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

2020

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“…Aging plays an important role in the progression of CKD [17]. As CKD brosis progresses, senescent cells express and secrete pro-brotic factors (TGF-β, CTGF, and so forth) and pro-in ammatory factors (IL-1β, IL-6, TNF-α, and so forth), which are senescence-associated secretory phenotype factors, thereby accelerating renal brosis [18,19]. At present, traditional Chinese medicine has achieved good results in treating renal brosis with fewer side effects.…”

Section: Discussionmentioning

confidence: 99%

Extract of Corallodiscus Flabellata Attenuates Renal Fibrosis in Aging Mice via the Wnt/β-catenin/RAS Signaling Pathway

Cao

Zeng

et al. 2020

Preprint

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Abstract Background: Renal fibrosis is a common pathological feature of chronic kidney disease (CKD). Aging accelerates renal fibrosis and further aggravates the process of CKD. Corallodiscus flabellata B. L. Burtt (C. flabellata) is a commonly used botanical drug in the Chinese population. However, few studies have reported its physiological effects. This study aimed to explore the effect of C. flabellata extract on renal fibrosis in aging mice and identify potentially active compounds. Methods: Using Senescence-accelerated mouse-prone 8 (SAMP8) mice and β-galactosidase (β-gal)-induced normal rat kidney epithelial cells (NRK-52E cells) as a model, to explore the mechanism of C. flabellata extract on senescence-related renal fibrosis, and initially clarified the material basis of C. flabellata. Results: The C. flabellata extract reduced the senescence and fibrosis of the kidneys in SAMP8 mice by activating nuclear factor erythroid 2–related factor 2 (Nrf2) to balance oxidative stress and inflammation, and interrupting the fibrinogen signaling in the Wnt/β-catenin/renin–angiotensin system. Moreover, 3,4-dihydroxyphenylethanol (SDC-0-14, 16) and (3,4-dihydroxyphenylethanol-8-O-[4-O-trans-caffeoyl-β-D-apiofuranosyl-(1→3)-β-D-glucopyranosyl (1→6)]-β-D-glucopyranoside (SDC-1-8) were isolated compounds from C. flabellata, which reduced the senescence of NRK-52E cells, and maybe the material basis for the function of C. flabellata. Conclusion: Our experiments illuminated that the extract of C. flabellata may improve the aging-related renal fibrosis through the Wnt/β-catenin/RAS pathway, and the material basis of its function may be SDC-0-14, 16 and SDC-1- 8.

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“…Tubule-derived EVs can mediate anti-inflammatory and proangiogenic actions, for example, secreting IL-10, which polarizes macrophages toward an M 2 phenotype, and galectin-1 and CD73, which promote Treg function (135,(150)(151)(152). Tubule-derived EVs can also directly interact with T lymphocytes through T-cell immunoglobulin-and mucin-containing molecules Tim-1 and Tim-4; interestingly, the same receptor Tim-1 (also called KIM-1) is expressed on renal tubular epithelial cells surface and mediates suppression of NF-κB (153).…”

Section: Renal Tubular Epithelial Cellsmentioning

confidence: 99%

Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft

et al. 2020

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Extracellular vesicles (EVs) are known immune-modulators exerting a critical role in kidney transplantation (KT). EV bioactive cargo includes graft antigens, costimulatory/inhibitory molecules, cytokines, growth factors, and functional microRNAs (miRNAs) that may modulate expression of recipient cell genes. As paracrine factors, neutrophil-and macrophage-derived EVs exert immunosuppressive and immune-stimulating effects on dendritic cells, respectively. Dendritic cell-derived EVs mediate alloantigen spreading and modulate antigen presentation to T lymphocytes. At systemic level, EVs exert pleiotropic effects on complement and coagulation. Depending on their biogenesis, they can amplify complement activation or shed complement inhibitors and prevent cell lysis. Likewise, endothelial-and platelet-derived EVs can exert procoagulant/prothrombotic effects and also promote endothelial survival and angiogenesis after ischemic injury. Kidney endothelial-and tubular-derived EVs play a key role in ischemia-reperfusion injury (IRI) and during the healing process; additionally, they can trigger rejection by inducing both alloimmune and autoimmune responses. Endothelial EVs have procoagulant/pro-inflammatory effects and can release sequestered self-antigens, generating a tissue-specific autoimmunity. Renal tubule-derived EVs shuttle pro-fibrotic mediators (TGF-β and miR-21) to interstitial fibroblasts and modulate neutrophil and T-lymphocyte influx. These processes can lead to peritubular capillary rarefaction and interstitial fibrosis-tubular atrophy. Different EVs, including those from mesenchymal stromal cells (MSCs), have been employed as a therapeutic tool in experimental models of rejection and IRI. These particles protect tubular and endothelial cells (by inhibition of apoptosis and inflammation-fibrogenesis or by inducing autophagy) and stimulate tissue regeneration (by triggering angiogenesis, cell proliferation, and migration). Finally, urinary and serum EVs represent potential biomarkers for delayed graft function (DGF) and acute rejection. In conclusion, EVs sustain an intricate crosstalk between graft tissue and innate/adaptive immune systems. EVs play a major role in allorecognition, IRI, autoimmunity, and alloimmunity and are promising as biomarkers and therapeutic tools in KT.

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Cellular Senescence in the Kidney

Cited by 168 publications

References 96 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

Extract of Corallodiscus Flabellata Attenuates Renal Fibrosis in Aging Mice via the Wnt/β-catenin/RAS Signaling Pathway

Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft

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