Glomerulosclerosis (scarring of the glomerulus, the “filter” of the kidney) is the end result of diverse forms of kidney injury. Significantly, most forms of glomerulosclerosis are associated with the final common pathway of damage and/or depletion of glomerular podocytes, the terminally differentiated visceral epithelial cells that maintain the kidney filtration barrier. By studying independent murine models of podocyte injury (HIV-1 transgenic mice, db/db FVBN/J diabetic mice and the Adriamycin nephropathy model), we have begun to gain insight into molecular pathways that are shared among various forms of nephropathy. To date, we have found that nephropathy loci impair mitochondrial homeostasis via disruption of mitochondrial DNA maintenance, or impairment of oxidative phosphorylation, confirming our initial hypothesis of a common final pathway leading to glomerulosclerosis.
Example of glomerular lesions in different models of nephropathy
(from Chan et. al. Kidney International 2009)