| Title |
Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance by suppressing NLRP3 inflammasome-mediated inflammation in type 2 diabetes rats
|
|---|---|
| Published in |
Stem Cell Research & Therapy, November 2017
|
| DOI | 10.1186/s13287-017-0668-1 |
| Pubmed ID | |
| Authors |
Xiaoya Sun, Haojie Hao, Qingwang Han, Xiaoyan Song, Jiejie Liu, Liang Dong, Weidong Han, Yiming Mu |
| Abstract |
Insulin resistance is one of the most common and important pathological features of type 2 diabetes (T2D). Recently, insulin resistance is increasingly considered to be associated with systemic chronic inflammation. Elevated levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in blood are predictive indicators of the development of T2D. Mesenchymal stem cell (MSC)-based therapies have been proven to have potential immunomodulation and anti-inflammatory properties through their paracrine effects; however, the mechanism for the anti-inflammatory effect of MSCs in enhancing insulin sensitivity is still uncertain. In the present experiment, we used HepG2 cells, a human hepatoma cell line, and a MSC-HepG2 transwell culturing system to investigate the anti-inflammatory mechanism of human umbilical cord-derived MSCs (UC-MSCs) under palmitic acid (PA) and lipopolysaccharide (LPS)-induced insulin resistance in vitro. Insulin resistance was confirmed by glycogen assay kit and glucose assay kit. Inflammatory factor release was detected by ELISA, gene expression was tested by quantitative real-time PCR, and insulin signaling activation was determined by western blotting analysis. The changes of inflammatory factors and insulin signaling protein were also tested in T2D rats injected with UC-MSCs. Treating HepG2 cells with PA-LPS caused NLRP3 inflammation activation, including overexpression of NLRP3 and caspase-1, and overproduction of IL-1β and IL-18 as well as TNF-α from HepG2 cells. The elevated levels of these inflammatory cytokines impaired insulin receptor action and thereby prevented downstream signaling pathways, exacerbating insulin resistance in HepG2 cells. Importantly, UC-MSCs cocultured with HepG2 could effectively alleviate PA and LPS-induced insulin resistance by blocking the NLRP3 inflammasome activation and inflammatory agents. Furthermore, knockdown of NLRP3 or IL-1β partially improved PA and LPS-induced insulin signaling impairments in the presence of UC-MSCs. Similarly, UC-MSC infusion significantly ameliorated hyperglycemia in T2D rats and decreased inflammatory activity, which resulted in improved insulin sensitivity in insulin target tissues. Our results indicated that UC-MSCs could attenuate insulin resistance and this regulation was correlated with their anti-inflammatory activity. Thus, MSCs might become a novel therapeutic strategy for insulin resistance and T2D in the near future. |
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 % |
|---|---|---|
| United States | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 81 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 81 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 9 | 11% |
| Student > Master | 9 | 11% |
| Student > Ph. D. Student | 9 | 11% |
| Student > Doctoral Student | 8 | 10% |
| Researcher | 4 | 5% |
| Other | 8 | 10% |
| Unknown | 34 | 42% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 13 | 16% |
| Biochemistry, Genetics and Molecular Biology | 11 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 6 | 7% |
| Agricultural and Biological Sciences | 3 | 4% |
| Nursing and Health Professions | 3 | 4% |
| Other | 7 | 9% |
| Unknown | 38 | 47% |
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 15 November 2017.
All research outputs
#15,482,347
of 23,007,053 outputs
Outputs from Stem Cell Research & Therapy
#1,350
of 2,429 outputs
Outputs of similar age
#206,116
of 329,244 outputs
Outputs of similar age from Stem Cell Research & Therapy
#47
of 80 outputs
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