Podocyte-derived extracellular vesicles mediate renal proximal tubule cells dedifferentiation via microRNA-221 in diabetic nephropathy

Hong, Soon-Kwang; Qiao, Jiao; Hu, Jinxiu; Li, Yanmei; Lin, Jiangong; Yu, Qun; Zhen, Junhui; Ma, Qiqi; Wang, Qianhui; Lv, Zhimei; Wang, Rong

doi:10.1016/j.mce.2020.111034

Cited by 41 publications

(25 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Exosomes from HG-treated macrophages could activate macrophages via the nuclear factor (NF)-kB pathway (27). Su et al (28) further demonstrated that exosomes from podocytes mediated the dedifferentiation of renal proximal tubule cells via miRNA-221 in DKD models. Other studies suggested beneficial effects of stem cells-derived exosomes in the treatment of DKD and role as biomarkers of urinary exosomes in DKD (29)(30)(31)(32)(33)(34)(35)(36).…”

mentioning

confidence: 99%

FOXO1-Mediated Downregulation of RAB27B Leads to Decreased Exosome Secretion in Diabetic Kidneys

Wen

et al. 2021

Diabetes

View full text Add to dashboard Cite

Exosomes have been implicated in diabetic kidney disease (DKD), but the regulation of exosomes in DKD is largely unknown. Here, we have verified the decrease of exosome secretion in DKD and unveiled the underlying mechanism. In Boston University mouse proximal tubule (BUMPT) cells, high-glucose (HG) treatment led to a significant decrease in exosome secretion, which was associated with specific downregulation of RAB27B, a key guanosine-5′-triphosphatase in exosome secretion. Overexpression of RAB27B restored exosome secretion in HG-treated cells, suggesting a role of RAB27B downregulation in the decrease of exosome secretion in DKD. To understand the mechanism of RAB27B downregulation, we conducted bioinformatics analysis that identified FOXO1 binding sites in the Rab27b gene promoter. Consistently, HG induced phosphorylation of FOXO1 in BUMPT cells, preventing FOXO1 accumulation and activation in the nucleus. Overexpression of nonphosphorylatable, constitutively active FOXO1 led to the upregulation of RAB27B and an increase in exosome secretion in HG-treated cells. In vivo, compared with normal mice, diabetic mice showed increased FOXO1 phosphorylation, decreased RAB27B expression, and reduced exosome secretion. Collectively, these results unveil the mechanism of exosome dysfunction in DKD where FOXO1 is phosphorylated and inactivated in DKD, resulting in RAB27B downregulation and the decrease of exosome secretion.

show abstract

mentioning

confidence: 99%

FOXO1-Mediated Downregulation of RAB27B Leads to Decreased Exosome Secretion in Diabetic Kidneys

Wen

et al. 2021

Diabetes

View full text Add to dashboard Cite

show abstract

“…Likewise, dedifferentiation of renal proximal tubular epithelial cells (PTECs) also plays a crucial role in interstitial fibrosis. After treatment with high glucose, podocyte-derived EVs induced dedifferentiation of PTECs through transporting miR-221-3p via the Wnt/β-catenin signaling pathway [10]. Moreover, evidence exists that implies TECs exosomal miR-19b-3p mediates the crosstalk between TECs and macrophages as well as contributes to the activation of M1 macrophages by targeting nuclear factor κB (NF-κB)/SOCS-1, which accounts for tubulointerstitial inflammation [50].…”

Section: Exosomes and Intercellular Communicationmentioning

confidence: 99%

“…All in all, it is urgent to explore new approaches to diagnose and treat DN. An increasing number of studies suggest that exosomes are involved in DN [9,10]. In our review, we summarize the potential roles of exosomes on the pathogenesis, biomarkers and therapies in DN.…”

mentioning

confidence: 99%

Exosomes: Advances, development and potential therapeutic strategies in diabetic nephropathy

Chen¹,

Zhang²,

Li³

et al. 2021

Metabolism

View full text Add to dashboard Cite

Exosomes, a major type of extracellular vesicles (EVs), are nanoscale vesicles excreted by almost all cell types via invagination of the endosomal membrane pathway. Exosomes play a crucial role in the mediation of intercellular communication both in health and disease, which can be ascribed to their capacity to be transported to neighboring or distant cells, thus regulating the biological function of recipient cells through cargos such as DNA, mRNA, proteins and microRNA. Diabetic nephropathy (DN) is a serious microvascular complication associated with diabetes mellitus as well as a significant cause of end-stage renal disease worldwide, which has resulted in a substantial economic burden on individuals and society. However, despite extensive efforts, therapeutic approaches that prevent the progression of DN do not exist, which implies new approaches are required. An increasing number of studies suggest that exosomes are involved in the pathophysiological processes associated with DN, which may potentially provide novel biomarkers and therapeutic targets for DN. Hence, this review summarizes recent advances involving exosome mechanisms in DN and their potential as biomarkers and therapeutic targets.

show abstract

“…Interestingly, podocyte EVs have been shown to regulate proximal tubular epithelial cells (PTECs) function in vitro. In particular, HG-podocyte EVs induced PTEC dedifferentiation through miRNA-221 and Wnt/β-catenin signaling [ 67 ], and the activation of fibrotic responses by increasing the expression of fibronectin, collagen type IV, p38, and the phosphorylation of Smad3 [ 68 ]. In addition, other authors observed PTECs apoptosis in response to HG-podocyte-EVs in a mechanism related to the differential encapsulation of 5 miRNAs [ 59 ].…”

Section: Biological Effects Of Evs On Renal Cellsmentioning

confidence: 99%

Urinary Extracellular Vesicles for Diabetic Kidney Disease Diagnosis

Saenz-Pipaon

Echeverria

Orbe

et al. 2021

JCM

View full text Add to dashboard Cite

Diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD) in developed countries, affecting more than 40% of diabetes mellitus (DM) patients. DKD pathogenesis is multifactorial leading to a clinical presentation characterized by proteinuria, hypertension, and a gradual reduction in kidney function, accompanied by a high incidence of cardiovascular (CV) events and mortality. Unlike other diabetes-related complications, DKD prevalence has failed to decline over the past 30 years, becoming a growing socioeconomic burden. Treatments controlling glucose levels, albuminuria and blood pressure may slow down DKD evolution and reduce CV events, but are not able to completely halt its progression. Moreover, one in five patients with diabetes develop DKD in the absence of albuminuria, and in others nephropathy goes unrecognized at the time of diagnosis, urging to find novel noninvasive and more precise early diagnosis and prognosis biomarkers and therapeutic targets for these patient subgroups. Extracellular vesicles (EVs), especially urinary (u)EVs, have emerged as an alternative for this purpose, as changes in their numbers and composition have been reported in clinical conditions involving DM and renal diseases. In this review, we will summarize the current knowledge on the role of (u)EVs in DKD.

show abstract

Podocyte-derived extracellular vesicles mediate renal proximal tubule cells dedifferentiation via microRNA-221 in diabetic nephropathy

Cited by 41 publications

References 40 publications

FOXO1-Mediated Downregulation of RAB27B Leads to Decreased Exosome Secretion in Diabetic Kidneys

FOXO1-Mediated Downregulation of RAB27B Leads to Decreased Exosome Secretion in Diabetic Kidneys

Exosomes: Advances, development and potential therapeutic strategies in diabetic nephropathy

Urinary Extracellular Vesicles for Diabetic Kidney Disease Diagnosis

Contact Info

Product

Resources

About