Glomerulosclerosis is associated with diabetes, hypertension and other conditions. It is the major cause of End Stage Renal Disease. It most commonly affects the older population. Glomerulosclerosis is associated with the selective loss of podocytes from the glomerulus in both type I and II diabetic glomerulosclerosis in man, as well as in the puromycin-treated rat. I present preliminary data from Fischer 344 rats to suggest that loss of podocytes also occurs in age-related glomerulosclerosis, and may be a common feature in all forms of glomerulosclerosis.
In specific aim 1, I will test the hypothesis that podocyte depletion predisposes to the development of glomerulosclerosis and that old Fischer 344 rats are more vulnerable to glomerulosclerosis because of reduced podocyte reserve. I will also test the hypothesis that even rats that do not spontaneously develop age-related glomerulosclerosis (Brown Norway) will do so if their podocytes are reduced in number.
In specific aim 2, I will test the hypothesis that calorie restriction and treatment with ACE inhibitors (both known to prevent age-related glomerulosclerosis) will also preserve podocyte numbers in the glomerulus.
In specific aim 3 I will begin to assess the molecular events associated with glomerular aging by performing gene expression profiling using Affymetrix GeneChips, to identify glomerular genes that are differentially expressed in animals that progress to glomerulosclerosis compared to those that do not. Finally I will put these changes into biological context by documenting gene expression in Fischer 344 rats throughout their life span. This analysis of glomerular aging associated with and without glomerulosclerosis will be complemented by course work and interaction with mentors and consultants designed to enhance my knowledge base and build towards my development as an independent investigator.
| Wiggins, Jocelyn E (2012) Aging in the glomerulus. J Gerontol A Biol Sci Med Sci 67:1358-64 |
| Wiggins, Jocelyn E; Patel, Sanjeevkumar R; Shedden, Kerby A et al. (2010) NFkappaB promotes inflammation, coagulation, and fibrosis in the aging glomerulus. J Am Soc Nephrol 21:587-97 |
| Wiggins, Jocelyn (2009) Podocytes and glomerular function with aging. Semin Nephrol 29:587-93 |
| Wiggins, Jocelyn E; Goyal, Meera; Wharram, Bryan L et al. (2006) Antioxidant ceruloplasmin is expressed by glomerular parietal epithelial cells and secreted into urine in association with glomerular aging and high-calorie diet. J Am Soc Nephrol 17:1382-7 |
| Wiggins, Jocelyn E; Goyal, Meera; Sanden, Silja K et al. (2005) Podocyte hypertrophy, ""adaptation,"" and ""decompensation"" associated with glomerular enlargement and glomerulosclerosis in the aging rat: prevention by calorie restriction. J Am Soc Nephrol 16:2953-66 |
