induction monotherapy with sirolimus has selected beneficial effects on glomerular and tubulointersititial injury in nephrotoxic serum nephritis
Clicks: 150
ID: 260233
2014
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
Emerging Content
30.0
/100
150 views
32 readers
AI Quality Assessment
Not analyzed
Readership in this journal
EmergingRanked #56 of 63 articles by views in Global change biology
Most read
Least read
Bar heights use a square-root scale.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
Lena Succar,1 Julia Lai-Kwon,1 David J Nikolic-Paterson,2 Gopala K Rangan1 1Centre for Transplant and Renal Research, Westmead Millennium Institute, University of Sydney, Westmead Hospital, Sydney, NSW, Australia; 2Department of Nephrology and Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC, Australia Background: The study aimed to test the hypothesis that therapeutic treatment with a mammalian target of rapamycin complex 1 inhibitor reduces renal cell proliferation and attenuates glomerular and tubulointerstitial injury in the early phase of nephrotoxic serum nephritis (NSN) in rats. Methods: Male Wistar-Kyoto rats received a single tail-vein injection of sheep anti-rat glomerular basement membrane serum (day 0) and were treated with vehicle or sirolimus (0.25 mg/kg/day by subcutaneous injection) from day 1 until day 14. Results: Treatment with sirolimus attenuated kidney enlargement by 41% (P<0.05), improved endogenous creatinine clearance by 50% (P<0.05), and reduced glomerular and tubulointerstitial cell proliferation by 53% and 70%, respectively, (P<0.05 compared to vehicle) in rats with NSN. In glomeruli, sirolimus reduced segmental fibrinoid necrosis by 69%, autologous rat immunoglobulin G deposition, glomerular capillary tuft enlargement, and periglomerular myofibroblast (α-smooth muscle actin-positive cells) accumulation (all P<0.05) but did not significantly affect glomerular crescent formation (P=0.15), macrophage accumulation (P=0.25), or the progression of proteinuria. In contrast, sirolimus preserved tubulointerstitial structure and attenuated all markers of injury (interstitial ED-1- and α-smooth muscle actin-positive cells and tubular vimentin expression; all P<0.05). By immunohistochemistry and Western blot analysis, sirolimus reduced the glomerular and tubulointerstitial expression of phosphorylated (Ser 235/236) S6-ribosomal protein (P<0.05). Conclusion: Induction monotherapy with sirolimus suppressed target of rapamycin complex 1 activation, renal cell proliferation, and injury during the early stages of rodent NSN, but the degree of histological protection was more consistent in the tubulointerstitium than the glomerular compartment. Keywords: glomerulonephritis, proliferation, crescentic, rapamycin, inflammation, kidney
| Reference Key |
l2014internationalinduction
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | ;Succar L;Lai-Kwon J;Nikolic-Paterson DJ;Rangan GK |
| Journal | Global change biology |
| Year | 2014 |
| DOI |
DOI not found
|
| URL | |
| Keywords |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.