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Abstract: TH-PO194

Tenascin C: A Pathogenic Factor in Diabetic Nephropathy?

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Prabhakar, Sharma S., Texas Tech University Health Sciences Center, Lubbock, Texas, United States
  • Deshmukh, Hemalata, Texas Tech University Health Sciences Center, Lubbock, Texas, United States
Background

Diabetic nephropathy (DN) is the most common cause of end stage renal disease in most parts of the world. The exact pathogenesis of DN is still unclear but renal fibrosis is a common end-result of all pathogenic mechanisms in DN. Tenascin C (TC) is an extra cellular matrix glycoprotein with pleotropic effects. TC was shown to interact with several growth factors such as VEGF, IGF, EGF, and TGF β, suggesting its potential role in fibrotic process. While Tenascin C has been incriminated in the progression of CKD, the role of TC in DN has not been studied. We hypothesize that given the potential biological effects of TC, it may be involved in the pathogenesis of DN.

Methods

To test our hypothesis we used ZSF rats, an established murine model of DN to examine the expression of TC in the kidneys. Both male and female rats were used and CD rats were used as non- diabetic controls. Rats were studied from 8th week to 40th week. The ZSF rats were provided a high fat high calorie diet (Purina 5008) to maintain hyperglycemia while control rats were given standard rat chow. All animals were euthanized at 40th week and kidneys harvested to prepare tissue homogenates. Urine samples were drawn at the start and end of the study period. Western blots were performed using TC specific antibody on the kidney homogenates to find the expression of TC.

Results

ZSF rats developed obesity, diabetes, hypertriglyceridemia, hypertension and proteinuric renal failure while CD rats remained nondiabetic without hypertension, obesity or kidney involvement. Male ZSF rats were heavier (650 gm vs 510 gm) and more hyperglycemic (295 mg/dl vs.210 mg/dl) than females while proteinuria and decreased kidney function were more severe in males versus female ZSF rats. Expression of TC was significantly increased in the kidneys of ZSF rats (males more than females) compared to CD rats.

Conclusion

We conclude that ZSF rats exhibit severe metabolic syndrome with stronger phenotypic characteristics in male vs. female ZSF rats. The increased renal expression of TC the ZSF kidneys suggests that they could be biomarkers of DN and may potentially have a pathogenic role.

Funding

  • Private Foundation Support