Objective: Exosomal microRNAs (miRNAs) are potential biomarkers for obesity, in which they regulate biological processes. Bariatric surgery has health benefits for patients with obesity; however, the mechanisms of these benefits are not clear. This study attempted to identify the exosomal miRNA signature associated with obesity and how it changed after bariatric surgery. Methods: Healthy volunteers (HVs) and nondiabetic patients with obesity were prospectively enrolled in the study. The study assessed the serum exosomal miRNA profiles of HVs and patients with obesity using RNA sequencing. To evaluate the effects of bariatric surgery, the study also analyzed exosomal miRNAs in patients 6 months after surgery. Results: RNA sequencing revealed differential expression of 72 exosomal miRNAs in patients with obesity compared with HVs and differential expression of 41 miRNAs in post-versus presurgery blood. Among the differentially expressed miRNAs, the study identified nine surgery-responsive miRNAs that were highly expressed in patients before surgery compared with HVs. Biological pathway analysis of the nine miRNAs indicated that they are likely involved in WNT, neurotrophin, and insulin signaling; the insulin receptor signaling cascade; and focal adhesion. Conclusions: Patients with obesity have a distinct exosomal miRNA expression profile compared with HVs. In addition, weight loss after surgery alters the exosomal miRNA profile of patients with obesity.
Background
Diabetic nephropathy (DN) is associated with high risk of cardiovascular disease and mortality. Exosomal microRNAs (miRNAs) regulate gene expression in a variety of tissues and play important roles in the pathology of various diseases. We hypothesized that the exosomal miRNA profile would differ between DN patients and patients without nephropathy.
Methods
We prospectively enrolled 74 participants, including healthy volunteers (HVs), diabetic patients without nephropathy, and those with DN. The serum exosomal miRNA profiles of participants were examined using RNA sequencing.
Results
The expression levels of 107 miRNAs differed between HVs and patients without DN, whereas the expression levels of 95 miRNAs differed between HVs and patients with DN. Among these miRNAs, we found 7 miRNAs (miR-1246, miR-642a-3p, let-7c-5p, miR-1255b-5p, let-7i-3p, miR-5010-5p, miR-150-3p) that were uniquely up-regulated in DN patients compared to HVs, and miR-4449 that was highly expressed in DN patients compared to patients without DN. A pathway analysis revealed that these eight miRNAs are likely involved in MAPK signaling, integrin function in angiogenesis, and regulation of the AP-1 transcription factor. Moreover, they were all significantly correlated with the degree of albuminuria.
Conclusions
Patients with DN have a different serum exosomal miRNA profile compared to HVs. These miRNAs may be promising candidates for the diagnosis and treatment of DN and cardiovascular disease.
Electronic supplementary material
The online version of this article (10.1186/s12967-019-1983-3) contains supplementary material, which is available to authorized users.
Our findings suggest that warfarin should be used carefully in hemodialysis patients, given the higher risk of hemorrhagic events and the lack of ability to prevent thromboembolic complications.
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