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Profile of Podocyte Translatome During Development of Type 2 and Type 1 Diabetic Nephropathy Using Podocyte-Specific TRAP mRNA RNA-seq
figure
posted on 2021-07-07, 17:33 authored by Yinqiu Wang, Aolei Niu, Yu Pan, Shirong Cao, Andrew S.Terker, Suwan Wang, Xiaofeng Fan, Cynthia L Toth, Marisol A Ramirez Solano, Danielle L Michell, Danielle Contreras, Ryan M Allen, Wanying Zhu, Quanhu Sheng, Agnes B. Fogo, Kasey C Vickers, Ming-Zhi Zhang, Raymond C. HarrisPodocyte injury is important in development of diabetic nephropathy (DN). Although several
studies have reported single
cell-based RNA-seq of podocytes in type 1 DN (T1DN), the podocyte translating mRNA profile in type 2 DN
(T2DN) has not been previously compared to
that of T1DN. We analyzed the podocyte translatome in T2DN in podocin-Cre; Rosa26fsTRAP;
eNOS-/-; db/db mice and compared it to streptozotocin-induced T1DN in podocin-Cre; Rosa26fsTRAP; eNOS-/-
mice utilizing Translating
Ribosome Affinity Purification (TRAP) and RNA-seq. Over 125 genes were highly enriched in the podocyte
ribosome. More podocyte
TRAP genes were differentially expressed in T2DN compared to T1DN. TGF-β
signaling pathway genes were upregulated while
MAPK pathway genes were downregulated only in T2DN while ATP binding and
cAMP-mediated signaling genes were
downregulated only in T1DN. Genes regulating actin filament organization and apoptosis increased while genes
regulating VEGFR signaling and glomerular
basement membrane components
decreased in both type 1 and type 2 diabetic podocytes. A number diabetes-induced genes not previously been
linked to podocyte injury were confirmed in both mouse and human DN. Differences and similarities in the podocyte
translatome in T2DN and T1DN can identify factors underlying the
pathophysiology of DN and novel therapeutic targets to treat diabetes-induced podocyte injury.