scholarly journals Profile of Podocyte Translatome During Development of Type 2 and Type 1 Diabetic Nephropathy Using Podocyte-Specific TRAP mRNA RNA-seq

2021 ◽  
Author(s):  
Yinqiu Wang ◽  
Aolei Niu ◽  
Yu Pan ◽  
Shirong Cao ◽  
Andrew S.Terker ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Mapk Pathway ◽  
Affinity Purification ◽  
Rna Seq ◽  
Podocyte Injury ◽  
Mrna Profile ◽  
Membrane Components ◽  
Basement Membrane Components

Podocyte 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) <u>has not been previously compared</u> to that of T1DN. <u>We</u> analyzed the podocyte translatome in T2DN in podocin-Cre; Rosa26<sup>fsTRAP</sup>; eNOS-/-; <i>db/db </i>mice and compared it to streptozotocin-induced T1DN in podocin-Cre; Rosa26<sup>fsTRAP</sup>; 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 <u>were confirmed in both</u> <u>mouse and human DN</u>. 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.

scholarly journals Profile of Podocyte Translatome During Development of Type 2 and Type 1 Diabetic Nephropathy Using Podocyte-Specific TRAP mRNA RNA-seq

2021 ◽  
Author(s):  
Yinqiu Wang ◽  
Aolei Niu ◽  
Yu Pan ◽  
Shirong Cao ◽  
Andrew S.Terker ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Mapk Pathway ◽  
Affinity Purification ◽  
Rna Seq ◽  
Podocyte Injury ◽  
Mrna Profile ◽  
Membrane Components ◽  
Basement Membrane Components

Podocyte 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) <u>has not been previously compared</u> to that of T1DN. <u>We</u> analyzed the podocyte translatome in T2DN in podocin-Cre; Rosa26<sup>fsTRAP</sup>; eNOS-/-; <i>db/db </i>mice and compared it to streptozotocin-induced T1DN in podocin-Cre; Rosa26<sup>fsTRAP</sup>; 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 <u>were confirmed in both</u> <u>mouse and human DN</u>. 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.

Profile of podocyte translatome during development of type 2 and type 1 diabetic nephropathy using podocyte-specific TRAP mRNA RNA-seq

Diabetes ◽  
2021 ◽  
pp. db210110
Author(s):  
Yinqiu Wang ◽  
Aolei Niu ◽  
Yu Pan ◽  
Shirong Cao ◽  
Andrew S. Terker ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Rna Seq

Maternal history of type 2 diabetes is associated with diabetic nephropathy in type 1 diabetic patients

2007 ◽  
Vol 33 (1) ◽  
pp. 37-43 ◽  
Author(s):  
S. Hadjadj ◽  
F. Duengler ◽  
F. Torremocha ◽  
G. Faure-Gerard ◽  
F. Bridoux ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Diabetic Patients ◽  
Maternal History ◽  
History Of ◽  
Type 1 Diabetic Patients

scholarly journals Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Junghyun Kim ◽  
Eunjin Shon ◽  
Chan-Sik Kim ◽  
Jin Sook Kim
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Glycated Haemoglobin ◽  
Protective Effects ◽  
Podocyte Injury ◽  
Podocyte Loss ◽  
Renal Changes ◽  
Hypoglycemic Drug ◽  
Antioxidant Effects

Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT) rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day) was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c), and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG) levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.

scholarly journals Advances in the Renin-Angiotensin-Aldosterone System: Relevance to Diabetic Nephropathy

2008 ◽  
Vol 8 ◽  
pp. 434-445 ◽  
Author(s):  
Audrey Koitka ◽  
Christos Tikellis
Keyword(s):  
Diabetic Nephropathy ◽  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Renal Disease ◽  
Converting Enzyme ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Angiotensin Type 2 Receptor

Hypertension is now recognized as a key contributory factor to the development and progression of kidney disease in both type 1 and type 2 diabetes. The renin angiotensin system (RAS) and its effector molecule angiotensin II, in particular, have a range of hemodynamic and nonhemodynamic effects that contribute not only to the development of hypertension, but also to renal disease. As a result, therapeutic inhibition of the RAS with angiotensin-converting enzyme inhibitors and/or selective angiotensin II type 1 receptor blockers has been proposed as a key strategy for reducing kidney damage beyond the expected effects one would observe with blood pressure reduction per se. Although the relationship between the RAS and the progression of diabetic renal disease has been known for many decades, recent advances have revealed a more complex paradigm with the discovery of a number of new components. Thus, further understanding of these new components of the renin angiotensin aldosterone system (RAAS), such as the angiotensin type 2 receptor subtype, angiotensin converting enzyme 2, and the recently cloned renin receptor, is likely to have therapeutic implications for disorders such as diabetic nephropathy, where interruption of the RAAS is widely used.

scholarly journals Automated image analysis of a glomerular injury marker desmin in spontaneously diabetic Torii rats treated with losartan

2014 ◽  
Vol 222 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Tetsuhiro Kakimoto ◽  
Kinya Okada ◽  
Yoshihiro Hirohashi ◽  
Raissa Relator ◽  
Mizue Kawai ◽  
...  
Keyword(s):  
Image Analysis ◽  
Diabetic Nephropathy ◽  
Early Stage ◽  
Automated Image Analysis ◽  
Angiotensin Ii Receptor Blocker ◽  
Analysis Method ◽  
Glomerular Injury ◽  
Image Analysis Method ◽  
Podocyte Injury

Diabetic nephropathy is a major complication in diabetes and a leading cause of end-stage renal failure. Glomerular podocytes are functionally and structurally injured early in diabetic nephropathy. A non-obese type 2 diabetes model, the spontaneously diabetic Torii (SDT) rat, is of increasing preclinical interest because of its pathophysiological similarities to human type 2 diabetic complications including diabetic nephropathy. However, podocyte injury in SDT rat glomeruli and the effect of angiotensin II receptor blocker treatment in the early stage have not been reported in detail. Therefore, we have evaluated early stages of glomerular podocyte damage and the beneficial effect of early treatment with losartan in SDT rats using desmin as a sensitive podocyte injury marker. Moreover, we have developed an automated, computational glomerulus recognition method and illustrated its specific application for quantitatively studying glomerular desmin immunoreactivity. This state-of-the-art method enabled automatic recognition and quantification of glomerular desmin-positive areas, eliminating the need to laboriously trace glomerulus borders by hand. The image analysis method not only enabled assessment of a large number of glomeruli, but also clearly demonstrated that glomerular injury was more severe in the juxtamedullary region than in the superficial cortex region. This applied not only in SDT rat diabetic nephropathy but also in puromycin aminonucleoside-induced nephropathy, which was also studied. The proposed glomerulus image analysis method combined with desmin immunohistochemistry should facilitate evaluations in preclinical drug efficacy studies as well as elucidation of the pathophysiology of diabetic nephropathy.

scholarly journals Homocysteinemia as a risk factor of diabetic nephropathy in children and adolescents

2008 ◽  
Vol 14 (4) ◽  
pp. 320-323
Author(s):  
Zh. V. Shutskaya
Keyword(s):  
Risk Factor ◽  
Diabetic Nephropathy ◽  
Children And Adolescents ◽  
Independent Risk Factor ◽  
Diabetes Type ◽  
Diabetes Type 1

This article summarizes data on homocysteinemia and its influence on vascular pathologic changes in patients with different diseases including diabetes type 1 and type 2. The role of homocystein as an independent risk factor for diabetic nephropathy in children and adolescents is discussed. The problem of homocysteinemia treatment is reviewed.

Lipotoxicity dysregulates the immunoproteasome in podocytes and kidneys in type 2 diabetes

2021 ◽  
Vol 320 (4) ◽  
pp. F548-F558
Author(s):  
Hyun Soon Lee ◽  
Ji Yeon Suh ◽  
Byeong-Choel Kang ◽  
Eugene Lee
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Fish Oil ◽  
Olive Oil ◽  
Renal Cortex ◽  
Diabetic Mice ◽  
Podocyte Injury ◽  
Type 2 Diabetic

In podocytes, PA rapidly induced immunoproteasome expression but ultimately decreased it, while OA and EPA restored the decreased immunoproteasome levels. In the renal cortex of type 2 diabetic mice, immunoproteasome expression was significantly decreased, whereas feeding of OA-rich olive oil or EPA-rich fish oil diets protected them against the reduced immunoproteasome expression and progression of diabetic nephropathy. Thus, lipotoxicity-induced podocyte injury with impaired immunoproteasome expression may be related to the pathogenesis of diabetic nephropathy.

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