Endothelial Microvesicles Induce Pulmonary Vascular Leakage and Lung Injury During Sepsis

Zheng, Danyang; Zhang, Jie; Zhang, Zisen; Kuang, Lei; Zhu, Yu; Wu, Yuzhang; Xue, Mingying; Zhao, Hongfeng; Duan, Chenyang; Liu, Liangming; Li, Tao

doi:10.3389/fcell.2020.00643

Cited by 17 publications

(25 citation statements)

References 44 publications

(67 reference statements)

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“…The damage of vascular endothelial barrier function is a critical pathophysiology process during the development of sepsis ( Koh et al, 2010 ), which will lead to multiple organ dysfunction syndrome (MODS) with high mortality. The vascular endothelium is an important organ of the body, which constitutes the fundamental barrier between blood and tissues ( Page and Liles, 2013 ; Zheng et al, 2020 ). However, there is still lack of targeted prevention and treatment of vascular leakage after sepsis.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Dexmedetomidine on the Vascular Endothelial Barrier Function by Inhibiting Mitochondrial Fission via ER/Mitochondria Contact

She

Zhu

Deng

et al. 2021

Front. Cell Dev. Biol.

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The damage of vascular endothelial barrier function induced by sepsis is critical in causing multiple organ dysfunctions. Previous studies showed that dexmedetomidine (Dex) played a vital role in protecting organ functions. However, whether Dex participates in protecting vascular leakage of sepsis and the associated underlying mechanism remains unknown yet. We used cecal ligation and puncture induced septic rats and lipopolysaccharide stimulated vascular endothelial cells (VECs) to establish models in vivo and in vitro, then the protective effects of Dex on the vascular endothelial barrier function of sepsis were observed, meanwhile, related mechanisms on regulating mitochondrial fission were further studied. The results showed that Dex could significantly reduce the permeability of pulmonary veins and mesenteric vessels, increase the expression of intercellular junction proteins, enhance the transendothelial electrical resistance and decrease the transmittance of VECs, accordingly protected organ functions and prolonged survival time in septic rats. Besides, the mitochondria of VECs were excessive division after sepsis, while Dex could significantly inhibit the mitochondrial fission and protect mitochondrial function by restoring mitochondrial morphology of VECs. Furthermore, the results showed that ER-MITO contact sites of VECs were notably increased after sepsis. Nevertheless, Dex reduced ER-MITO contact sites by regulating the polymerization of actin via α2 receptors. The results also found that Dex could induce the phosphorylation of the dynamin-related protein 1 through down-regulating extracellular signal-regulated kinase1/2, thus playing a role in the regulation of mitochondrial division. In conclusion, Dex has a protective effect on the vascular endothelial barrier function of septic rats. The mechanism is mainly related to the regulation of Drp1 phosphorylation of VECs, inhibition of mitochondrial division by ER-MITO contacts, and protection of mitochondrial function.

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Section: Introductionmentioning

confidence: 99%

Protective Effects of Dexmedetomidine on the Vascular Endothelial Barrier Function by Inhibiting Mitochondrial Fission via ER/Mitochondria Contact

She

Zhu

Deng

et al. 2021

Front. Cell Dev. Biol.

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“…Sprague-Dawley (SD) rats of either sex (weighting 190–215g) were provided by the Animal Center of the Army Medical Center. The cecal ligation and puncture (CLP) procedure was induced as described previously [ 28 , 29 ]. Briefly, rats were anesthetized by sodium pentobarbital (25mg/kg, IP), and a 2-cm incision was made along the linea alba, then the end of the cecum was exposed and ligated, and the ligated cecum was punctured by a triangular pyramid, and the above operations were carried out under aseptic conditions.…”

Section: Methodsmentioning

confidence: 99%

“…MMVs were harvested from the supernatant of cultured cells as described previously [ 28 ]. Briefly, when MSCs grew to 75% confluence, cells were washed with PBS and cultured in exosome-free medium with 1% serum for 48h.…”

Section: Methodsmentioning

confidence: 99%

“…MMVs were characterized by flow cytometry as described previously [ 28 ]. Briefly, CD29 (BD, America), CD73 (BD, America), CD90 (BD, America), CD105 (BD, America), CD105 (BD, America), and AnnexinV (BD, America) were applied to identify MMVs, where CD45 was the negative marker for MMVs and the others were positive markers for MMVs.…”

Section: Methodsmentioning

confidence: 99%

“…MMVs were characterized by TEM as described previously [ 28 ]. Briefly, the MMV pellet was fixed by 2.5% glutaraldehyde for 24h at 4°C.…”

Section: Methodsmentioning

confidence: 99%

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Mesenchymal stem cell-derived microvesicles improve intestinal barrier function by restoring mitochondrial dynamic balance in sepsis rats

et al. 2021

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Background Sepsis is a major cause of death in ICU, and intestinal barrier dysfunction is its important complication, while the treatment is limited. Recently, mesenchymal stem cell-derived microvesicles (MMVs) attract much attention as a strategy of cell-free treatment; whether MMVs are therapeutic in sepsis induced-intestinal barrier dysfunction is obscure. Methods In this study, cecal ligation and puncture-induced sepsis rats and lipopolysaccharide-stimulated intestinal epithelial cells to investigate the effect of MMVs on intestinal barrier dysfunction. MMVs were harvested from mesenchymal stem cells and were injected into sepsis rats, and the intestinal barrier function was measured. Afterward, MMVs were incubated with intestinal epithelial cells, and the effect of MMVs on mitochondrial dynamic balance was measured. Then the expression of mfn1, mfn2, OPA1, and PGC-1α in MMVs were measured by western blot. By upregulation and downregulation of mfn2 and PGC-1α, the role of MMVs in mitochondrial dynamic balance was investigated. Finally, the role of MMV-carried mitochondria in mitochondrial dynamic balance was investigated. Results MMVs restored the intestinal barrier function by improving mitochondrial dynamic balance and metabolism of mitochondria. Further study revealed that MMVs delivered mfn2 and PGC-1α to intestinal epithelial cells, and promoted mitochondrial fusion and biogenesis, thereby improving mitochondrial dynamic balance. Furthermore, MMVs delivered functional mitochondria to intestinal epithelial cells and enhanced energy metabolism directly. Conclusion MMVs can deliver mfn2, PGC-1α, and functional mitochondria to intestinal epithelial cells, synergistically improve mitochondrial dynamic balance of target cells after sepsis, and restore the mitochondrial function and intestinal barrier function. The study illustrated that MMVs might be a promising strategy for the treatment of sepsis.

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Genistein, a Soybean Isoflavone, Promotes Wound Healing by Enhancing Endothelial Progenitor Cell Mobilization in Rats with Hemorrhagic Shock

Peng

Zhu

et al. 2023

Advanced Biology

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Severe trauma and hemorrhaging are often accompanied by delayed cutaneous wound healing. Soybean isoflavone is a natural phytoestrogen that has attracted great attention due to its protective effects against various injuries. Endothelial progenitor cells (EPCs) are precursor cells with directional differentiation characteristics. This study is to determine whether genistein (GEN), an isoflavone in soybean products, benefits wound healing in hemorrhagic shock (HS) rats by promoting EPC homing and to investigate the underlying mechanisms. In this study, it is found that GEN promotes skin wound healing in HS rats, which is due at least partly to the mobilization of endogenous EPCs to the injury site via angiotensin II (Ang‐II), stromal cell‐derived factor‐1alpha (SDF‐1α), and transforming growth factor beta(TGF‐β) signaling.

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Endothelial Microvesicles Induce Pulmonary Vascular Leakage and Lung Injury During Sepsis

Cited by 17 publications

References 44 publications

Protective Effects of Dexmedetomidine on the Vascular Endothelial Barrier Function by Inhibiting Mitochondrial Fission via ER/Mitochondria Contact

Protective Effects of Dexmedetomidine on the Vascular Endothelial Barrier Function by Inhibiting Mitochondrial Fission via ER/Mitochondria Contact

Mesenchymal stem cell-derived microvesicles improve intestinal barrier function by restoring mitochondrial dynamic balance in sepsis rats

Genistein, a Soybean Isoflavone, Promotes Wound Healing by Enhancing Endothelial Progenitor Cell Mobilization in Rats with Hemorrhagic Shock

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