2. Academic Validation
  3. Pyroptosis and ferroptosis induced by mixed lineage kinase 3 (MLK3) signaling in cardiomyocytes are essential for myocardial fibrosis in response to pressure overload

Pyroptosis and ferroptosis induced by mixed lineage kinase 3 (MLK3) signaling in cardiomyocytes are essential for myocardial fibrosis in response to pressure overload

  • Cell Death Dis. 2020 Jul 24;11(7):574. doi: 10.1038/s41419-020-02777-3.
Junyan Wang 1 2 3,  Bo Deng 1 2 3,  Qing Liu 1 2 3,  Yusheng Huang 1 2 3 4,  Weitao Chen 1 2 3,  Jing Li 1 2 3,  Zheng Zhou 2 3,  Lu Zhang 1 2 3,  Birong Liang 1 2 3,  Jiaqi He 1 2 3,  Zixin Chen 1 2 3 4,  Cui Yan 1 2 3,  Zhongqi Yang 1 2 3 4 5,  Shaoxiang Xian 6 7 8 9 10,  Lingjun Wang 11 12 13 14 15
Affiliations

Affiliations

  • 1 The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
  • 2 The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
  • 3 Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
  • 4 Guangzhou Key Laboratory of Chinese Medicine for Prevention and Treatment of Chronic Heart Failure, Guangzhou, 510405, China.
  • 5 National Clinical Research Base of Traditional Chinese Medicine, Guangzhou, 510405, China.
  • 6 The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. shaoxiangx@hotmail.com.
  • 7 The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. shaoxiangx@hotmail.com.
  • 8 Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. shaoxiangx@hotmail.com.
  • 9 Guangzhou Key Laboratory of Chinese Medicine for Prevention and Treatment of Chronic Heart Failure, Guangzhou, 510405, China. shaoxiangx@hotmail.com.
  • 10 National Clinical Research Base of Traditional Chinese Medicine, Guangzhou, 510405, China. shaoxiangx@hotmail.com.
  • 11 The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. smu868@163.com.
  • 12 The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. smu868@163.com.
  • 13 Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. smu868@163.com.
  • 14 Guangzhou Key Laboratory of Chinese Medicine for Prevention and Treatment of Chronic Heart Failure, Guangzhou, 510405, China. smu868@163.com.
  • 15 National Clinical Research Base of Traditional Chinese Medicine, Guangzhou, 510405, China. smu868@163.com.
PMID: 32710001 DOI: 10.1038/s41419-020-02777-3
Abstract

Chronic heart failure (CHF) is the final outcome of many cardiovascular diseases, and is a severe health issue faced by the elderly population. Mixed Lineage Kinase 3 (MLK3), a member of MAP3K family, is associated with aging, inflammation, oxidative stress, and related diseases, such as CHF. MLK3 has also been reported to play an important role in protecting against cardiomyocyte injury; however, its function in myocardial fibrosis is unknown. To investigate the role of MLK3 in myocardial fibrosis, we inhibited the expression of MLK3, and examined cardiac function and remodeling in TAC mice. In addition, we assessed the expression of MLK3 protein in ventricular cells and its downstream associated protein. We found that MLK3 mainly regulates NF-κB/NLRP3 signaling pathway-mediated inflammation and that Pyroptosis causes myocardial fibrosis in the early stages of CHF. Similarly, MLK3 mainly regulates the JNK/p53 signaling pathway-mediated oxidative stress and that Ferroptosis causes myocardial fibrosis in the advanced stages of CHF. We also found that promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC. These results suggest the Pyroptosis and Ferroptosis induced by MLK3 signaling in cardiomyocytes are essential for adverse myocardial fibrosis, in response to pressure overload. Furthermore, miR-351, which has a protective effect on ventricular remodeling in heart failure caused by pressure overload, may be a key target for the regulation of MLK3.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z