Semi-automated quantitative image analysis of podocyte desmin immunoreactivity as a sensitive marker for acute glomerular damage in the rat puromycin aminonucleoside nephrosis (PAN) model.
Glomerular visceral epithelial cells or podocytes are crucial for glomerular function and podocyte damage has been shown to be inevitably involved in glomerulopathies. Podocytes react to injury in a stereotypic manner. Accompanying morphologic changes is altered expression of intermediate filaments. Desmin is strongly upregulated in injured podocytes. Here we show, that semi-automated quantitative image analysis of desmin immunoreactivity in glomerula is a valid and sensitive marker for acute podocyte and thus glomerular damage in the puromycin aminonucleoside nephrosis (PAN) model in the rat with the potential of an efficacy marker in animal disease models as well as a toxicity marker for podocyte injury. Additionally, a panel of acknowledged urinary kidney biomarkers was evaluated for utility in the PAN model.
Herrmann
Annika
A
Non-clinical Drug Safety and Metabolic Diseases Departments, F. Hoffmann-La Roche Ltd., Switzerland. annika.herrmann@roche.com
Tozzo
Effie
E
Funk
Jürgen
J
D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D003893:Desmin / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007090:Image Interpretation, Computer-Assisted; D007150:Immunohistochemistry; D007677:Kidney Function Tests; D008297:Male; D009401:Nephrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011692:Puromycin Aminonucleoside / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index
D015415:Biomarkers; D003893:Desmin; D011692:Puromycin Aminonucleoside