| Title |
CTGF siRNA ameliorates tubular cell apoptosis and tubulointerstitial fibrosis in obstructed mouse kidneys in a Sirt1-independent manner
|
|---|---|
| Published in |
Drug Design, Development and Therapy, July 2015
|
| DOI | 10.2147/dddt.s86748 |
| Pubmed ID | |
| Authors |
Yunzhuo Ren, Chunyang Du, Li Yan, Jingying Wei, Haijiang Wu, Yonghong Shi, Huijun Duan |
| Abstract |
Transforming growth factor-β1 (TGF-β1) plays an important role in the pathogenesis and progression of chronic kidney disease. Connective tissue growth factor (CTGF) is a critical fibrogenic mediator of TGF-β1. Mammalian sirtuin 1 (Sirt1) is reported to attenuate renal fibrosis by inhibiting the TGF-β1 pathway. This study was designed to detect whether the delivery of CTGF siRNA in vivo directly ameliorates renal fibrosis. Furthermore, the relationship with Sirt1 underlying the protective effect of CTGF siRNA on interstitial fibrosis and apoptosis was explored. Here, we report that the expressions of CTGF and TGF-β1 were increased while Sirt1 expression and activity were both dramatically decreased in mouse kidneys with unilateral ureteral obstruction. Recombinant human TGF-β1 treatment in HK-2 cells increased CTGF levels and remarkably decreased Sirt1 levels and was accompanied by apoptosis and release of fibrosis-related factors. Recombinant human CTGF stimulation also directly induced apoptosis and fibrosis. The CTGF siRNA plasmid ameliorated tubular cell apoptosis and tubulointerstitial fibrosis, but did not affect Sirt1 expression and activity both in vivo and in vitro. Furthermore, overexpression of Sirt1 abolished TGF-β1-induced cell apoptosis and fibrosis, while Sirt1 overexpression suppressed CTGF expression via stimulation by TGF-β1. This study provides evidence that treatment strategies involving the delivery of siRNA targeting potentially therapeutic transgenes may be efficacious. Our results suggest that the decrease in Sirt1 is associated with the upregulated expression of CTGF in renal fibrosis, and may aid in the design of new therapies for the prevention of renal fibrosis. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| India | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
| Scientists | 1 | 50% |
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 % |
|---|---|---|
| Student > Doctoral Student | 3 | 25% |
| Student > Ph. D. Student | 2 | 17% |
| Student > Bachelor | 2 | 17% |
| Librarian | 1 | 8% |
| Unspecified | 1 | 8% |
| Other | 0 | 0% |
| Unknown | 3 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 3 | 25% |
| Unspecified | 1 | 8% |
| Biochemistry, Genetics and Molecular Biology | 1 | 8% |
| Immunology and Microbiology | 1 | 8% |
| Agricultural and Biological Sciences | 1 | 8% |
| Other | 2 | 17% |
| Unknown | 3 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 April 2016.
All research outputs
#16,048,009
of 25,374,917 outputs
Outputs from Drug Design, Development and Therapy
#925
of 2,268 outputs
Outputs of similar age
#146,210
of 277,613 outputs
Outputs of similar age from Drug Design, Development and Therapy
#66
of 157 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,268 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has gotten more attention than average, scoring higher than 55% of its peers.
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We're also able to compare this research output to 157 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.