Abstract: FR-PO736
Senescent Podocytes in Human Obesity Release Urinary Extracellular Vesicles (uEVs)
Session Information
- Glomerular Diseases: Mechanisms and Podocyte Biology
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Al Saeedi, Mina H., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Zhu, Xiang yang, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Denic, Aleksandar, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Rule, Andrew D., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Xing, Li, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Zhang, Lei, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Tang, Hui, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Jordan, Kyra L., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Lerman, Amir, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Fidler, Mary E., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Kukla, Aleksandra, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Lerman, Lilach O., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
Group or Team Name
- Nephrology and Hypertension.
Background
Obesity induces cellular senescence, which is implicated in renal disease progression. Senescent cells are characterized by the expression of senescence markers like P19, a cyclin-dependent kinase inhibitor, and possibly pro-inflammatory monocyte chemoattractant protein (MCP)-1. However, whether podocytes marked by podocalyxin (Podxl)+ undergo senescence in obesity is unclear. We hypothesized that patients with obesity show elevated levels of P19+/Podxl+/MCP1+ uEVs suggestive of podocyte senescence
Methods
Blood and urine samples were collected from 21 obese (OB) and 10 lean subjects for uEVs quantification (NanoSight) and characterization (Flow Cytometry) for P19, Podoxl, and MCP1 expression (Fig1). Their fraction out of total uEVs was correlated with body mass index (BMI), urinary protein, kidney injury molecule (KIM)-1, and insulin levels
Results
OB subjects had elevated BMI but preserved renal function (Table). The total uEV number was similar in OB and lean, but the fractions of P19+/Podxl+ and P19+/Podoxl+/MCP1+ uEVs were higher in OB and directly correlated with BMI. P19+/Podoxl+/MCP1+ uEVs also correlated with urine protein, KIM1, and insulin levels (Fig2)
Conclusion
Senescent podocytes in obese subjects with preserved renal function shed uEVs in proportion to obesity severity. The uEVs fraction shed by a subset of inflamed (MCP1+) senescent podocytes further correlates with renal injury markers. These may serve as early markers of glomerular senescence and guide the management of patients with obesity
Table. Demographics
| Parameter | Lean | OB |
| Age, Yrs. | 47±15 | 48±12 |
| Sex, M/F | 3/7 | 7/14 |
| BMI, Kg/m2 | 25±1 | 44±6* |
| Serum Creatinine, mg/dl | 0.9(0.7,1.2) | 0.8(0.6,1.4) |
| eGFR, ml/min/1.73m2 | 90±10 | 96±17 |
| Urine Protein, mg/mmol | 32(2,57) | 66(3,189) |
Mean ± SD or median (min, max) *P<0.05 vs. Lean
Funding
- NIDDK Support