miR-6869-5p Transported by Plasma Extracellular Vesicles Mediates Renal Tubule Injury and Renin-Angiotensin System
Huan-Huan Liu1, Xia-Qing Li1, Jin-Feng Liu1
1Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Abstract:
Obesity increases the risk of other diseases, including kidney disease. Local renal tubular renin-angiotensin system (RAS) activation may play a role in obesity-associated kidney disease. Extracellular vehicles (EVs) transmit necessary information in obesity and cause remote organ damage, but the mechanism is unclear. The aim of the study was to investigate whether the plasma EVs cargo miR-6869-5p causes RAS activation and renal tubular damage. We isolated plasma EVs from obese and lean subjects and analyzed differentially-expressed miRNAs using RNA-seq. Then, EVs were co-cultured with human proximal renal tubular epithelial cells (PTECs) in vitro. Immunohistochemical pathology was used to assess the degree of RAS activation and tubule injury in vivo. The tubule damage-associated protein and RAS activation components were detected by Western blot. Obesity led to renal tubule injury and RAS activation in humans and mice. Obese-EVs induce RAS activation and renal tubular injury in PTECs. Importantly, miR-6869-5p-treated PTECs caused RAS activation and renal tubular injury, similar to Obese-EVs. Inhibiting miR-6869-5p decreased RAS activation and renal tubular damage. Our findings indicate that plasma Obese-EVs induce renal tubule injury and RAS activation via miR-6869-5p transport. Thus, miR-6869-5p in plasma Obese-EVs could be a therapeutic target for local RAS activation in obesity-associated kidney disease.
Insights
Obesity-associated kidney disease involves local renin-angiotensin system (RAS) activation. Plasma extracellular vesicles (EVs) from obese individuals deliver miR-6869-5p, causing RAS activation and kidney tubule damage.
Area of Science:
- Nephrology
- Molecular Biology
- Obesity Research
Background:
- Obesity is a significant risk factor for kidney disease.
- Local renin-angiotensin system (RAS) activation is implicated in obesity-related kidney damage.
- The role of extracellular vesicles (EVs) in mediating obesity's effects on organs is not fully understood.
Purpose of the Study:
- To investigate if plasma EVs from obese individuals carry microRNA-6869-5p (miR-6869-5p).
- To determine if this cargo activates the RAS and causes renal tubular injury.
- To explore miR-6869-5p as a potential therapeutic target.
Main Methods:
- Plasma EVs were isolated from obese and lean subjects.
- RNA sequencing identified differentially expressed miRNAs in EVs.
- EVs were co-cultured with human proximal renal tubular epithelial cells (PTECs) in vitro; RAS activation and tubule injury were assessed in vivo and via Western blot.
Main Results:
- Obesity was associated with renal tubule injury and RAS activation in humans and mice.
- EVs from obese individuals (Obese-EVs) induced RAS activation and PTEC injury.
- miR-6869-5p treatment mimicked Obese-EV effects; inhibition reduced injury, confirming its role.
Conclusions:
- Plasma Obese-EVs promote renal tubule injury and RAS activation through miR-6869-5p.
- miR-6869-5p within Obese-EVs is a potential therapeutic target for obesity-associated kidney disease.
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