Wei Zheng, Yun Qian, Shuai Chen, Hongjiang Ruan, Cunyi Fan
Abstract
Dysregulation of autophagy plays a pivotal role in fibrosis in multiple organs. However, the role of autophagy in peritendinous fibrosis is not well understood. Here, we hypothesize that autophagy plays a protective role in preventing adhesion formation. In a rat model of tendon injury, we observed dysregulated autophagy during excessive extracellular matrix deposition. Pharmacological induction of autophagy by rapamycin markedly alleviated the severity of peritendinous fibrosis in vivo. In NIH/3T3 fibroblasts and tenocytes, transforming growth factor β1 (TGF-β1) markedly activated myofibroblasts and increased collagen synthesis. Addition of rapamycin activated autophagy, reduced collagen synthesis, and suppressed myofibroblast activation. In vitro experiments also showed that rapamycin decreased cell proliferation and increased the number of cells arrested in G0/G1 phase. However, following pretreatment with the autophagy inhibitor 3-methyladenine (3-MA), rapamycin was unable to repress the fibrotic changes induced by TGF-β1. Autophagy related protein 5 (Atg5) RNA interference in fibroblasts also abolished the protective effects of rapamycin in vitro. In conclusion, our results point to rapamycin as a potential treatment strategy in the prevention of peritendinous fibrosis after tendon injury.
Pharmacology, Toxicology and Pharmaceutical Science
1
6%
Computer Science
1
6%
Nursing and Health Professions
1
6%
Other
2
11%
Unknown
8
44%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 20 December 2021.
All research outputs
#13,162,991
of 22,729,647 outputs
Outputs from Frontiers in Pharmacology
#3,738
of 15,963 outputs
Outputs of similar age
#163,032
of 325,990 outputs
Outputs of similar age from Frontiers in Pharmacology
#99
of 390 outputs
Altmetric has tracked 22,729,647 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 15,963 research outputs from this source. They receive a mean Attention Score of 4.9. This one has done well, scoring higher than 75% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 325,990 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 390 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 74% of its contemporaries.
