microRNA-15b-5p shuttled by mesenchymal stem cell-derived extracellular vesicles protects podocytes from diabetic nephropathy via downregulation of VEGF/PDK4 axis

Zhao, Tiantian; Jin, Qingsong; Kong, Lili; Zhang, Dongdong; Teng, Yaqin; Lin, Liangyan; Yao, Xiaoyan; Jin, Yongjun; Li, Minglong

doi:10.1007/s10863-021-09919-y

Cited by 22 publications

(11 citation statements)

References 31 publications

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“…It is possible that a subset of these altered miRNA contributes to the enhanced immunomodulatory function. In preliminary analyses of some of the highly expressed miRNAs that are also differentially expressed, candidates such as miR-15b ( 46 ), miR-19b ( 47 ) and miR-22 ( 48 , 49 ) stand out due to their established roles in immunomodulation. For example, miR-22 is a negative regulator of the NLRP3 inflammasome pathway ( 50 ) and has established anti-inflammatory function ( 50 , 51 ).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles From TNFα Preconditioned MSCs: Effects on Immunomodulation and Bone Regeneration

et al. 2022

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Mesenchymal stem cells show remarkable versatility and respond to extracellular and micro environmental cues by altering their phenotype and behavior. In this regard, the MSC’s immunomodulatory properties in tissue repair are well documented. The paracrine effects of MSCs in immunomodulation are, in part, attributable to their secreted extracellular vesicles (EVs). When MSCs migrate to the wound bed, they are exposed to a myriad of inflammatory signals. To understand their response to an inflammatory environment from an EV perspective, we sought to evaluate the effects of the inflammatory cytokine TNFα on MSC EV mediated immunomodulation. Our results indicate that while the physical characteristics of the EVs remain unchanged, the TNFα preconditioned MSC EVs possess enhanced immunomodulatory properties. In vitro experiments using polarized (M1 and M2) primary mouse macrophages indicated that the preconditioned MSC EVs suppressed pro-inflammatory (M1) markers such as IL-1β and iNOS and elevated reparatory (M2) markers such as Arg1 and CD206. When evaluated in vivo in a rat calvarial defect model, the TNFα preconditioned MSC EVs reduced inflammation at 1-, 3- and 7-days post wounding resulting in the subsequent enhanced bone formation at 4- and 8-weeks post wounding possibly by modulation of oncostatin M (OSM) expression. An analysis of EV miRNA composition revealed significant changes to anti-inflammatory miRNAs in the preconditioned MSC EVs hinting at a possible role for EV derived miRNA in the enhanced immunomodulatory activity. Overall, these results indicate that MSC exposure to inflammatory signals influence the MSC EV’s immunomodulatory function in the context of tissue repair. The specific function of TNFα preconditioned MSC EV miRNAs in immunomodulatory control of bone regeneration merits further investigation.

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Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles From TNFα Preconditioned MSCs: Effects on Immunomodulation and Bone Regeneration

et al. 2022

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“…[ 43 ] Inhibition of extracellular matrix and mesangial cell proliferation: Chronic hyperglycemia and excessive development of advanced glycation end products (AGEs) produce anomalies in VEGFA synthesis and release in many signaling pathways, including inflammation, excessive ROS production, TGF- and CTGF activation, and foot process effacement, and disrupts VEGFA overexpression and inhibits mesangial cell proliferation and extracellular matrix proliferation. [ 44 ]…”

Section: Discussionmentioning

confidence: 99%

The effect and safety of low-dose Tripterygium wilfordii in patients with type 2 diabetic nephropathy: A meta-analysis

Chen

Feng

et al. 2022

Medicine

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Background: This review aims to assess the efficacy and safety of low-dose Tripterygium wilfordii Hook F (TWHF) in treating type 2 diabetic nephropathy (DN) and provide high-level evidence supporting its normalized application. Methods: Seven electronic databases were queried to locate trials that qualify. Randomized controlled trials (RCTs) about low-dose TWHF long-term treatment of type 2 DN are included. After data extraction and quality evaluation of the clinical studies that met the inclusion criteria, a meta-analysis was performed using RevMan 5.4 and Stata 14. Results: A total of 23 RCTs were included. For the patients in the trial group, the effective rate [confidence interval (CI), odd ratio] [odd ratio = 1.38, 95% CI (1.22–1.56), P < .001], albumin [standard mean difference (SMD) = 0.58, 95% CI (0.18–0.98), P = .004], 24-hour urine total protein [SMD = −1.329, 95% CI = (−1.647 to −1.012), P < .001], serum creatinine [SMD = −0.64, 95% CI = (−0.86 to −0.31), P < .001], and the untoward effect [RR = 2.43 95% CI = (1.23–4.82), P = .01] were significantly higher than those in the control group. However, in white blood cell [Weighted mean difference = −0.27, 95% CI (−0.54 to 0.01), P = .06] and blood urea nitrogen [Weighted mean difference = −0.11, 95% CI (−0.42 to 0.21), z = 0.67, P = .50], none of the differences were significant compared with the control group. Conclusion: This suggests that low-dose TWHF positively affects patients with type 2 DN after a long course of treatment. Although there are some side effects, symptoms can improve after medication suspension or symptomatic treatment. Limited by the methodological quality of the included studies, this conclusion needs to be verified by more large-sample RCTs with rigorous design and long-term follow-up.

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“…In clinical practice, circulating exomiRs isolated from urine or serum have great potential as promising biomarkers in DKD [97]. However, exosomes contain typical markers, such as TSG101, Alix, integrins, and tetraspanins, such as CD63, CD9, and CD81 [98].…”

Section: Endocrine Journal Advance Publicationmentioning

confidence: 99%

Therapeutic role of mesenchymal stem cells (MSCs) in diabetic kidney disease (DKD)

Liu

2022

Endocr J

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microRNA-15b-5p shuttled by mesenchymal stem cell-derived extracellular vesicles protects podocytes from diabetic nephropathy via downregulation of VEGF/PDK4 axis

Cited by 22 publications

References 31 publications

Extracellular Vesicles From TNFα Preconditioned MSCs: Effects on Immunomodulation and Bone Regeneration

Extracellular Vesicles From TNFα Preconditioned MSCs: Effects on Immunomodulation and Bone Regeneration

The effect and safety of low-dose Tripterygium wilfordii in patients with type 2 diabetic nephropathy: A meta-analysis

Therapeutic role of mesenchymal stem cells (MSCs) in diabetic kidney disease (DKD)

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