Myeloid-derived growth factor improves pyroptosis in H9c2 cells induced by high glucose

Yu ZHANG; Yan WANG; Ranzun ZHAO; Zhimei QIU; Xianping LONG; Chaofu LI; Wenming CHEN; Bei SHI

doi:10.16016/j.1000-5404.202011210

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Myeloid-derived growth factor improves pyroptosis in H9c2 cells induced by high glucose

更新时间：2026-01-09

- Myeloid-derived growth factor improves pyroptosis in H9c2 cells induced by high glucose
- Journal of Third Military Medical University Vol. 43, Issue 10, Pages: 923-929(2021)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the Regional Program of Natural Science Foundation of China(81860061);the Regional Program of National Natural Science Foundation of China(82060061);the "Hundred-Level" Cultivation Project of High-Level Innovative Talents in Guizhou Province (2015-4025);the Start-up Fund for Master's Scientific Research of the Affiliated Hospital of Zunyi Medical University(院字(2016)51号)
- DOI：10.16016/j.1000-5404.202011210
  CLC：
- Received：22 November 2020，
  
  Published：30 May 2021
- 稿件说明：
移动端阅览
Yu ZHANG, Yan WANG, Ranzun ZHAO, et al. Myeloid-derived growth factor improves pyroptosis in H9c2 cells induced by high glucose[J]. Journal of Third Military Medical University, 2021, 43(10): 923-929.
DOI：

Yu ZHANG, Yan WANG, Ranzun ZHAO, et al. Myeloid-derived growth factor improves pyroptosis in H9c2 cells induced by high glucose[J]. Journal of Third Military Medical University, 2021, 43(10): 923-929. DOI： 10.16016/j.1000-5404.202011210.

摘要

Abstract

Objective

To investigate whether myeloid-derived growth factor (Mydgf) can improve cardiomyocyte pyroptosis induced by hyperglycemia by regulating nucleotide-binding domain-like receptor protein 3 (NLRP3).

Methods

Cultured rat cardiomyocyte H9c2 cells were divided into 4 groups: normal group (Nor)

high glucose group (HG

50 mmol/L glucose for 24 h)

Mydgf group (25 ng/mL recombinant Mydgf protein for 12 h

followed by 50 mmol/L glucose for 24 h)

and necrosulfonamide group (NSA

32 μmol/L necrosulfonamide for 0.5 h

followed by 50 mmol/L glucose for 24 h). Western blotting was used to detect the protein levels of cleaved Caspase-1

NLRP3

apoptosis-related speckle-like proteins (ACS) and gasdermin D (GSDMD). The secretions of IL-1β and IL-18 in cell culture medium were detected by ELISA. CCK-8 assay was used to detect the effect of Mydgf or NLRP3 on the viability of H9c2 cells. Lentiviral vector carrying NLRP3 and enhanced green fluorescent protein (EGFP) (NLRP3-EGFP) and empty viral vector (EGFP) were transfected into H9c2 cells respectively

and the changes of pyroptosis related indexes were detected by recovery experiments.

Results

Western blot results showed that the expression levels of pyroptosis related proteins

cleaved Caspase 1

ACS

NLRP3 and GSDMD were significantly higher in the HG group than the Nor group (

0.05). Mydgf treatment effectively inhibited the expression of a

bove proteins (

0.05)

but the inhibitory efficiencies were lower than that in the NSA group (

0.05). ELISA demonstrated that the secretions of IL-1β and IL-18 were increased in the HG group (

0.05)

but decreased in the Mydgf group (

0.05)

and more significantly reduced in the NSA group (

0.05). CCK-8 assay indicated that Mydgf at a concentration of below 25 ng/mL had no significant effect on the viability of H9c2 cells

while when the concentration above 25 ng/mL

the treatment significantly decreased the cell viability (

0.05). Compared with the control group

overexpression of NLRP3 significantly decreased H9c2 cells viability under the condition of HG. Transfection of lentiviral vector NLRP3-EGFP resulted in obvious increases in the mRNA and protein expression of NLRP3 (

0.05)

but that of empty vector had no such effects (

0.05). In the recovery experiment

Western blot results showed that in the high-glucose environment

the expression level of NLRP3

ASC

and cleaved Caspase-1 were significantly increased (

0.05)

and the secretions of IL-1β and IL-18 were also significantly enhanced in the Mydgf +NLRP3-EGFP group compared with the Mydgf group (

0.05).

Conclusion

Mydgf may ameliorate cardiomyocyte pyroptosis induced by hyperglycemia by inhibiting NLRP3.

关键词

Keywords

references

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