↓ Skip to main content

Blockade of TGF-β/Smad signaling by the small compound HPH-15 ameliorates experimental skin fibrosis

Overview of attention for article published in Arthritis Research & Therapy, March 2018
Altmetric Badge

Mentioned by

twitter
2 tweeters

Citations

dimensions_citation
12 Dimensions

Readers on

mendeley
27 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
Blockade of TGF-β/Smad signaling by the small compound HPH-15 ameliorates experimental skin fibrosis
Published in
Arthritis Research & Therapy, March 2018
DOI 10.1186/s13075-018-1534-y
Pubmed ID
Authors

Vu Huy Luong, Takenao Chino, Noritaka Oyama, Takashi Matsushita, Yoko Sasaki, Dai Ogura, Shin-ichiro Niwa, Tanima Biswas, Akiyuki Hamasaki, Mikako Fujita, Yoshinari Okamoto, Masami Otsuka, Hironobu Ihn, Minoru Hasegawa

Abstract

Transforming growth factor-β (TGF-β)/Smad signaling is well known to play a critical role in the pathogenesis of systemic sclerosis (SSc). We previously developed an artificial molecule, the histidine-pyridine-histidine ligand derivative HPH-15, which may have an antifibrotic effect. The purpose of the present study was to clarify the effects of this drug in human skin fibroblasts and in a preclinical model of SSc. The effects of HPH-15 on expression of extracellular matrix components and TGF-β signaling in human dermal fibroblasts were analyzed. The antifibrotic properties of HPH-15 and its mechanisms were also examined in a bleomycin-induced skin fibrosis mouse model. HPH-15 suppressed the TGF-β-induced phosphorylation of Smad3 and inhibited the expression of collagen I, fibronectin 1, connective tissue growth factor, and α-smooth muscle actin induced by TGF-β in cultured human skin fibroblasts. In the bleomycin-induced skin fibrosis model, oral administration of HPH-15 protected against the development of skin fibrosis and ameliorated established skin fibrosis. Additionally, HPH-15 suppressed the phosphorylation of Smad3 in various cells, including macrophages in the bleomycin-injected skin. Further, in the treated mice, dermal infiltration of proinflammatory macrophages (CD11b+Ly6Chi) and M2 profibrotic macrophages (CD11b+CD204+ or CD11b+CD206+) was significantly decreased during the early and late stages, respectively. HPH-15 treatment resulted in decreased messenger RNA (mRNA) expression of the M2 macrophage markers arginase 1 and Ym-1 in the skin, whereas it inversely augmented expression of Friend leukemia integration 1 and Krüppel-like factor 5 mRNAs, the transcription factors that repress collagen synthesis. No apparent adverse effects of HPH-15 were found during the treatment. HPH-15 may inhibit skin fibrosis by inhibiting the phosphorylation of Smad3 in dermal fibroblasts and possibly in macrophages. Our results demonstrate several positive qualities of HPH-15, including oral bioavailability, a good safety profile, and therapeutic effectiveness. Thus, this TGF-β/Smad inhibitor is a potential candidate therapeutic for SSc clinical trials.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 27 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 26%
Student > Ph. D. Student 5 19%
Student > Postgraduate 2 7%
Student > Doctoral Student 2 7%
Student > Master 1 4%
Other 4 15%
Unknown 6 22%
Readers by discipline Count As %
Medicine and Dentistry 6 22%
Biochemistry, Genetics and Molecular Biology 4 15%
Agricultural and Biological Sciences 4 15%
Pharmacology, Toxicology and Pharmaceutical Science 2 7%
Immunology and Microbiology 2 7%
Other 3 11%
Unknown 6 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 25 March 2018.
All research outputs
#9,742,018
of 12,706,057 outputs
Outputs from Arthritis Research & Therapy
#1,680
of 2,070 outputs
Outputs of similar age
#190,317
of 273,760 outputs
Outputs of similar age from Arthritis Research & Therapy
#1
of 1 outputs
Altmetric has tracked 12,706,057 research outputs across all sources so far. This one is in the 20th percentile – i.e., 20% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,070 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one is in the 15th percentile – i.e., 15% of its peers scored the same or lower than it.
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 273,760 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 24th percentile – i.e., 24% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them