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Abstract: TH-PO921

LC-MS/MS-Based Proteomics Analysis Reveals Correlations Between Kidney Injury and Mediators of Vascular Pathology, Inflammation, and Oxidative Stress in Diabetic African American Men

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Ongeri, Elimelda Moige, North Carolina A&T State University, Greensboro, North Carolina, United States
  • Smith, Aldeisha Dr, North Carolina A&T State University, Greensboro, North Carolina, United States
  • Ahmed, Faihaa, North Carolina A&T State University, Greensboro, North Carolina, United States
  • Newman, Heather A., North Carolina A&T State University, Greensboro, North Carolina, United States
  • Jegede, Olugbemiga E., Cone Health, Greensboro, North Carolina, United States
  • Newman, Robert H., North Carolina A&T State University, Greensboro, North Carolina, United States
  • Harrison, Scott H., North Carolina A&T State University, Greensboro, North Carolina, United States
Background

The prevalence of diabetic nephropathy (DN) is disproportionately high among minority ethnic groups in the US. African American (AA) men are especially underrepresented in research to identify biomarkers of DN which are then used for the development of diagnostic tools and therapeutics targets. The goal of the current study was to identify biomarkers present in the serum of diabetic AA men which correlate with kidney injury and thus gain insights on the cellular and molecular mechanisms underlying the progression of DN in this population.

Methods

Fasting blood and urine samples were obtained from AA men aged 18-65 years; (i) non-diabetic controls (n=22), (ii) diabetics (n=65), and (iii) diabetics with diagnosed kidney disease (n=13). Assays for urinary albumin, creatinine, kidney injury molecule 1 (KIM-1) and neutrophil gelatinase associated lipocalin (NGAL) were used for evaluation of kidney function. The serum samples were depleted of abundant proteins then subjected to global LC-MS/MS-based analysis. The data were searched using Proteome Discoverer 2.2 utilizing Sequest HT search algorithm. Linear regression modeling was conducted for screening changes in association with urinary albumin and creatinine ratio (UACR), and odds and fold changes calculated across groups.

Results

29 of the identified proteins correlated with UACR. Among these are proteins involved in vascular pathology (vasorin, fibulin-1, neuropilin), inflammation (protein disulfide-isomerase, tenascin-X, vascular cell adhesion protein 1), oxidative stress (sulfhydryl oxidase 1), and ECM/ fibrosis (tenascin-X, fibulin-1).

Conclusion

The data suggest that the progression of kidney injury in AA men is associated with vascular pathology, inflammation, and oxidative stress. Vasorin has distinct glomerular localization and is down-regulated during vessel repair. Reversal of vasorin down-regulation inhibits TGF-β signaling diminishing injury-induced vascular lesions. AGEs, which are linked to DN, suppress the expression of neuropilin-1 in podocytes. Tenascin X, localizes in the mesangium of kidney glomeruli, activates latent TGF-β, and induces TFG-β/Smad signaling. Increased levels of fibulin-1 also associate with impaired kidney function.

Funding

  • NIDDK Support