↓ Skip to main content

Pentoxifylline Attenuates Proteinuria in Anti-Thy1 Glomerulonephritis via Downregulation of Nuclear Factor-κB and Smad2/3 Signaling

Overview of attention for article published in Molecular Medicine, April 2015
Altmetric Badge

Citations

dimensions_citation
14 Dimensions

Readers on

mendeley
12 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Pentoxifylline Attenuates Proteinuria in Anti-Thy1 Glomerulonephritis via Downregulation of Nuclear Factor-κB and Smad2/3 Signaling
Published in
Molecular Medicine, April 2015
DOI 10.2119/molmed.2015.00023
Pubmed ID
Authors

Yung-Ming Chen, Wen-Chih Chiang, Yalin Yang, Chun-Fu Lai, Kwan-Dun Wu, Shuei-Liong Lin

Abstract

Anti-Thy1 glomerulonephritis is a rat nephritis model closely simulating human mesangial proliferative glomerulonephritis. It affects primarily the mesangium, yet displaying substantial proteinuria during the course. This study investigated the molecular signals underlying proteinuria in this disease, and the modulation of which by the known anti-proteinuric agent, pentoxifylline. Male Wistar rats were randomly divided into a control group and nephritic groups with or without treatment with IMD-0354 (an IκB kinase inhibitor), SB431542 (an activin receptor-like kinase inhibitor), or pentoxifylline. Kidney sections were prepared for histological examinations. Glomeruli were isolated for mRNA and protein analysis. Urine samples were collected for protein and nephrin quantitation. One day after nephritis induction, proteinuria developed together with ultrastructural changes of the podocyte and downregulation of podocyte mRNA and protein expression. These were associated with upregulation of TNF-α and TGF-β/activins mRNAs and activation of NF-κB p65 and Smad2/3. IMD-0354 attenuated proteinuria on day 1 while SB431542 decreased proteinuria on days 3 and 5, in association with partial restoration of downregulated podocyte mRNA and protein expression. Pentoxifylline attenuated proteinuria and nephrinuria through the course, plus inhibition of p-NF-κB p65 (day 1) and p-Smad2/3 (day 5), and partial reversal of downregulated podocyte mRNA and protein. Our data show that the pathogenesis of proteinuria in anti-Thy1 glomerulonephritis involves TNF-α and TGF-β/activin pathways, and the evolution of this process can be attenuated by pentoxifylline via downregulation of NF-κB and Smad signals and restoration of podocyte component of the glomerular filtration barrier.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 12 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 12 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 25%
Student > Doctoral Student 2 17%
Student > Postgraduate 2 17%
Student > Ph. D. Student 1 8%
Professor > Associate Professor 1 8%
Other 1 8%
Unknown 2 17%
Readers by discipline Count As %
Medicine and Dentistry 8 67%
Social Sciences 1 8%
Biochemistry, Genetics and Molecular Biology 1 8%
Unknown 2 17%