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Background: Albuminuria is a hallmark of diabetic kidney disease (DKD) that promotes its progression, leading to renal fibrosis. Renal macrophage function is complex and influenced by macrophage metabolic status. However, the metabolic state of diabetic renal macrophages and the impact of albuminuria on the macrophage metabolic state are poorly understood. Methods: Extracellular vesicles (EVs) from tubular epithelial cells (HK-2) were evaluated using transmission electron microscopy, nanoparticle tracking analysis and western blotting. Glycolytic enzyme expression in macrophages co-cultured with HSA-treated HK-2 cell-derived EVs was detected using RT-qPCR and western blotting. The potential role of EV-associated HIF-1α in the mediation of glycolysis was explored in HIF-1α siRNA pre-transfected macrophages co-cultured with HSA-treated HK-2 cell-derived EVs, and the extent of HIF-1α hydroxylation was measured using western blotting. Additionally, we injected db/db mice with EVs via the caudal vein twice a week for 4 weeks. Renal macrophages were isolated using CD11b microbeads, and immunohistofluorescence was applied to confirm the levels of glycolytic enzymes and HIF-1α in these macrophages. Results: Glycolysis was activated in diabetic renal macrophages after co-culture with HSA-treated HK-2 cells. Moreover, HSA-treated HK-2 cell-derived EVs promoted macrophage glycolysis both in vivo and in vitro. Inhibition of glycolysis activation in macrophages using the glycolysis inhibitor 2-DG decreased the expression of both inflammatory and fibrotic genes. Mechanistically, EVs from HSA-stimulated HK-2 cells were found to accelerate macrophage glycolysis by stabilizing HIF-1α. We also found that several miRNAs and lncRNAs, which have been reported to stabilize HIF-1α expression, were increased in HSA-treated HK-2 cell-derived EVs. Conclusion: Our study suggested that albuminuria induced renal macrophage glycolysis through tubular epithelial cell-derived EVs by stabilizing HIF-1α, indicating that regulation of macrophage glycolysis may offer a new treatment strategy for DKD patients, especially those with macroalbuminuria. [ABSTRACT FROM AUTHOR]

Background: Albuminuria is a hallmark of diabetic kidney disease (DKD) that promotes its progression, leading to renal fibrosis. Renal macrophage function is complex and influenced by macrophage metabolic status. However, the metabolic state of diabetic renal macrophages and the impact of albuminuria on the macrophage metabolic state are poorly understood. Methods: Extracellular vesicles (EVs) from tubular epithelial cells (HK-2) were evaluated using transmission electron microscopy, nanoparticle tracking analysis and western blotting. Glycolytic enzyme expression in macrophages co-cultured with HSA-treated HK-2 cell-derived EVs was detected using RT-qPCR and western blotting. The potential role of EV-associated HIF-1α in the mediation of glycolysis was explored in HIF-1α siRNA pre-transfected macrophages co-cultured with HSA-treated HK-2 cell-derived EVs, and the extent of HIF-1α hydroxylation was measured using western blotting. Additionally, we injected db/db mice with EVs via the caudal vein twice a week for 4 weeks. Renal macrophages were isolated using CD11b microbeads, and immunohistofluorescence was applied to confirm the levels of glycolytic enzymes and HIF-1α in these macrophages. Results: Glycolysis was activated in diabetic renal macrophages after co-culture with HSA-treated HK-2 cells. Moreover, HSA-treated HK-2 cell-derived EVs promoted macrophage glycolysis both in vivo and in vitro. Inhibition of glycolysis activation in macrophages using the glycolysis inhibitor 2-DG decreased the expression of both inflammatory and fibrotic genes. Mechanistically, EVs from HSA-stimulated HK-2 cells were found to accelerate macrophage glycolysis by stabilizing HIF-1α. We also found that several miRNAs and lncRNAs, which have been reported to stabilize HIF-1α expression, were increased in HSA-treated HK-2 cell-derived EVs. Conclusion: Our study suggested that albuminuria induced renal macrophage glycolysis through tubular epithelial cell-derived EVs by stabilizing HIF-1α, indicating that regulation of macrophage glycolysis may offer a new treatment strategy for DKD patients, especially those with macroalbuminuria. [ABSTRACT FROM AUTHOR]

[Display omitted] Adipose tissues (AT) are an important endocrine organ that secretes various functional adipokines, peptides, non-coding RNAs, and acts on AT themselves or other distant tissues or organs through autocrine, paracrine, or endocrine manners. An accumulating body of evidence has suggested that many adipokines play an important role in liver metabolism. Besides the traditional adipokines such as adiponectin and leptin, many novel adipokines have recently been identified to have regulatory effects on the liver. Additionally, AT can produce extracellular vesicles (EVs) that act on peripheral tissues. However, under pathological conditions, such as obesity and diabetes, dysregulation of adipokines is associated with functional changes in AT, which may cause liver diseases. In this review, we focus on the newly discovered adipokines and EVs secreted by AT and highlight their actions on the liver under the context of obesity, nonalcoholic fatty liver diseases (NAFLD), and some other liver diseases. Clarifying the action of adipokines and adipose tissue-derived EVs on the liver would help to identify novel therapeutic targets or biomarkers for metabolic diseases. [ABSTRACT FROM AUTHOR]

• High-performance tracking of BEVs in living systems has been realized with an AIEgen. • The probe can illuminate BEVs and shows remarkable merits over traditional methods. • The spatial and temporal distributions of BEVs within host can be clearly visualized. The nano-sized, membrane-enclosed bacterial extracellular vesicles (BEVs) released by bacteria are now regarded as important mediators involved in various physiological and pathological processes of human. To elucidate their roles in bacteria-to-host communication, methods for visualizing and tracking of these nano-vesicles are crucial, but ideal means are lacking currently. In this work, we report the development of a bioprobe, DPASP, for BEV bioimaging with superior performance. DPASP can target BEVs with boosted fluorescence due to its aggregation-induced emission (AIE) attribute, which allows BEV labeling with a high signal-to-background ratio. For BEV imaging, DPASP outperforms the commercial dyes in terms of labeling efficiency, retention time, photostability, and biocompatibility. The applications of DPASP in studying the spatial and temporal distributions of E. coli -derived BEVs within living cells and mice were also demonstrated. The approach developed here provides a valuable tool to better understand the roles of BEVs in health and diseases. [ABSTRACT FROM AUTHOR]

• High-performance tracking of BEVs in living systems has been realized with an AIEgen. • The probe can illuminate BEVs and shows remarkable merits over traditional methods. • The spatial and temporal distributions of BEVs within host can be clearly visualized. The nano-sized, membrane-enclosed bacterial extracellular vesicles (BEVs) released by bacteria are now regarded as important mediators involved in various physiological and pathological processes of human. To elucidate their roles in bacteria-to-host communication, methods for visualizing and tracking of these nano-vesicles are crucial, but ideal means are lacking currently. In this work, we report the development of a bioprobe, DPASP, for BEV bioimaging with superior performance. DPASP can target BEVs with boosted fluorescence due to its aggregation-induced emission (AIE) attribute, which allows BEV labeling with a high signal-to-background ratio. For BEV imaging, DPASP outperforms the commercial dyes in terms of labeling efficiency, retention time, photostability, and biocompatibility. The applications of DPASP in studying the spatial and temporal distributions of E. coli -derived BEVs within living cells and mice were also demonstrated. The approach developed here provides a valuable tool to better understand the roles of BEVs in health and diseases. [ABSTRACT FROM AUTHOR]