Multiple Metabolic Hits Converge on CD36 Scavenger Receptor as Novel Mediator of
Tubular Epithelial Apoptosis in Diabetic Nephropathy
Authors Katalin Susztak*, Emilio Ciccone†, Kumar Sharma†, ‡, Erwin P. Böttinger*, ‡
Submitted By Erwin Bottinger on 5/3/2004
Status Published
Journal PLoS medicine / Public Library of Science
Year 2005
Date Published 2/1/2005
Volume : Pages 2 : 152 - 161
PubMed Reference 15737001
Abstract Diabetic nephropathy (DNP) is a common chronic complication of type 1 and type 2
diabetes mellitus and the most common cause of end-stage renal failure. While
DNP manifests with albuminuria and characteristic diabetic glomerulopathy, its
progression to renal failure correlates best with tubular epithelial
degeneration (TED) and interstitial fibrosis (IF). However, mechanisms leading
to TED in DNP remain poorly understood. We found that expression of class B
scavenger receptor CD36 coincided with proximal tubular epithelial cells (PTEC)
apoptosis and TED in human DNP. High ambient glucose stimulated cell surface
expression of CD36 in PTEC. CD36 expression was necessary and sufficient to
mediate PTEC apoptosis induced by glycated albumins (AGE-BSA) and free fatty
acid (FFA) through activation of proapoptotic p38 MAPK signaling. In contrast,
paucity of expression of Cd36 in PTEC in diabetic mice with diabetic
glomerulopathy was associated with absence of tubular apoptosis and normal
tubular epithelium. Mouse PTEC lacked Cd36 and were resistant to AGE-BSA induced
apoptosis. Recombinant expression of CD36 in mouse PTECs confered susceptibility
to AGE-BSA-induced apoptosis. In conclusion, our findings suggest a novel role
for CD36 as essential mediator of proximal tubular apoptosis in human DNP. As
glucose induced CD36 expression in PTECs, and since increased CD36 mediated
AGE-BSA and/or FFA induced PTEC apoptosis, we propose a new two-step metabolic
hit model for TED, a hallmark of progression of human diabetic nephropathy.


Cd36CD36 antigen
Mapk14mitogen activated protein kinase 14
Scarb1scavenger receptor class B, member 1