Macrophage‐derived exosomal
            <scp>miR</scp>
            ‐195a‐5p impairs tubular epithelial cells mitochondria in acute kidney injury mice

Yuan, Longhui; Yang, Jingchao; Liu, Fei; Li, Lan; Liu, Jingping; Chen, Younan; Cheng, Jun; Liu, Yanrong; Yuan, Yujia

doi:10.1096/fj.202200644r

Cited by 10 publications

(4 citation statements)

References 75 publications

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“…Exosomes contain a variety of cargoes, including miRNAs, other RNA species, lipids, and proteins. Previously, based on the miRNA profile, we demonstrated that miR-195a-5p in Mφ-derived exosomes from AKI mice was increased, while blockade of miR-195a-5p inhibited mitochondrial damage in AKI mice 23 . Here, the level of miR-195a-5p in Mφ from Atg7 Δmye mice was 55.08 ± 6.34 fold higher than that in Mφ from WT mice and was further elevated after cisplatin injection (Fig.…”

Section: Exosomes Derived From Autophagy-deficient Mφ Impaired Mitoch...mentioning

confidence: 91%

Autophagy-deficient macrophages exacerbate cisplatin-induced mitochondrial dysfunction and kidney injury via miR-195a-5p-SIRT3 axis

Yuan,

Yang

et al. 2024

Nat Commun

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Macrophages (Mφ) autophagy is a pivotal contributor to inflammation-related diseases. However, the mechanistic details of its direct role in acute kidney injury (AKI) were unclear. Here, we show that Mφ promote AKI progression via crosstalk with tubular epithelial cells (TECs), and autophagy of Mφ was activated and then inhibited in cisplatin-induced AKI mice. Mφ-specific depletion of ATG7 (Atg7Δmye) aggravated kidney injury in AKI mice, which was associated with tubulointerstitial inflammation. Moreover, Mφ-derived exosomes from Atg7Δmye mice impaired TEC mitochondria in vitro, which may be attributable to miR-195a-5p enrichment in exosomes and its interaction with SIRT3 in TECs. Consistently, either miR-195a-5p inhibition or SIRT3 overexpression improved mitochondrial bioenergetics and renal function in vivo. Finally, adoptive transfer of Mφ from AKI mice to Mφ-depleted mice promotes the kidney injury response to cisplatin, which is alleviated when Mφ autophagy is activated with trehalose. We conclude that exosomal miR-195a-5p mediate the communication between autophagy-deficient Mφ and TECs, leading to impaired mitochondrial biogenetic in TECs and subsequent exacerbation of kidney injury in AKI mice via miR-195a-5p-SIRT3 axis.

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Section: Exosomes Derived From Autophagy-deficient Mφ Impaired Mitoch...mentioning

confidence: 91%

Autophagy-deficient macrophages exacerbate cisplatin-induced mitochondrial dysfunction and kidney injury via miR-195a-5p-SIRT3 axis

Yuan,

Yang

et al. 2024

Nat Commun

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“…miR-195a-5p is upregulated in a model of cisplatin-induced AKI. Macrophages transport miR-195a-5p through exosomes, resulting in tubular mitochondrial dysfunction and cell damage ( 116 ).…”

Section: Crosstalk Between Ptecs and Other Interstitial Cellsmentioning

confidence: 99%

Crosstalk between proximal tubular epithelial cells and other interstitial cells in tubulointerstitial fibrosis after renal injury

Guo,

Cui,

Jiao

et al. 2024

Front. Endocrinol.

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The energy needs of tubular epithelial components, especially proximal tubular epithelial cells (PTECs), are high and they heavily depend on aerobic metabolism. As a result, they are particularly vulnerable to various injuries caused by factors such as ischemia, proteinuria, toxins, and elevated glucose levels. Initial metabolic and phenotypic changes in PTECs after injury are likely an attempt at survival and repair. Nevertheless, in cases of recurrent or prolonged injury, PTECs have the potential to undergo a transition to a secretory state, leading to the generation and discharge of diverse bioactive substances, including transforming growth factor-β, Wnt ligands, hepatocyte growth factor, interleukin (IL)-1β, lactic acid, exosomes, and extracellular vesicles. By promoting fibroblast activation, macrophage recruitment, and endothelial cell loss, these bioactive compounds stimulate communication between epithelial cells and other interstitial cells, ultimately worsening renal damage. This review provides a summary of the latest findings on bioactive compounds that facilitate the communication between these cellular categories, ultimately leading to the advancement of tubulointerstitial fibrosis (TIF).

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“… 181 Subsequent studies identified that EVs derived from infiltrated macrophages upon I/R-AKI contain miR-195a-5p and miR-155, which induce renal tubular cell injury and AKI progression. 182 , 183 In summary, there is evidence that EVs derived from immune cells or blood cells could contribute to physiological and pathological processes in kidney homeostasis and disease.…”

Section: Non-stem Cell-derived Ev In Akimentioning

confidence: 99%

Systems Approaches to Cell Culture-Derived Extracellular Vesicles for Acute Kidney Injury Therapy: Prospects and Challenges

Lundy,

Szomolay,

Liao

2024

Function

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Acute kidney injury (AKI) is a heterogeneous syndrome, comprising diverse aetiologies of kidney insults which result in high mortality and morbidity if not well-managed. Although great efforts have been made to investigate underlying pathogenic mechanisms of AKI, there are limited therapeutic strategies available. Extracellular vesicles (EV) are membrane-bound vesicles secreted by various cell types which can serve as cell-free therapy through transfer of bioactive molecules. In this review, we first overview the AKI syndrome and EV biology, with a particular focus on the technical aspects and therapeutic application of cell culture-derived EVs. Secondly, we illustrate how multi-omic approaches to EV miRNA, protein and genomic cargo analysis can yield new insights into their mechanisms of action and address unresolved questions in the field. We then summarise major experimental evidence regarding the therapeutic potential of EVs in AKI, which we subdivide into stem cell and non-stem cell-derived EVs. Finally, we highlight the challenges and opportunities related to clinical translation of animal studies into human patients.

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Macrophage‐derived exosomal miR ‐195a‐5p impairs tubular epithelial cells mitochondria in acute kidney injury mice

Cited by 10 publications

References 75 publications

Autophagy-deficient macrophages exacerbate cisplatin-induced mitochondrial dysfunction and kidney injury via miR-195a-5p-SIRT3 axis

Autophagy-deficient macrophages exacerbate cisplatin-induced mitochondrial dysfunction and kidney injury via miR-195a-5p-SIRT3 axis

Crosstalk between proximal tubular epithelial cells and other interstitial cells in tubulointerstitial fibrosis after renal injury

Systems Approaches to Cell Culture-Derived Extracellular Vesicles for Acute Kidney Injury Therapy: Prospects and Challenges

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