2. Academic Validation
  3. Mycoplasma pneumoniae-induced Kawasaki disease via PINK1/Parkin-mediated mitophagy

Mycoplasma pneumoniae-induced Kawasaki disease via PINK1/Parkin-mediated mitophagy

  • Exp Cell Res. 2024 Aug 15;441(2):114182. doi: 10.1016/j.yexcr.2024.114182.
Chengyi Wang 1,  Huijie Zhang 2,  Jinyan Zhang 3,  Zesheng Hong 3,  Chong Miao 4,  Tengyang Wang 5,  Han Lin 5,  Yinglin Li 6,  Guanghua Liu 7
Affiliations

Affiliations

  • 1 College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, PR China; Department of Pediatrics, Fujian Children's Hospital(Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, PR China; College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Maternity and Child Health Hospital, Fuzhou 350001, PR China.
  • 2 Department of Pediatrics, Fujian Children's Hospital(Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, PR China; College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Maternity and Child Health Hospital, Fuzhou 350001, PR China.
  • 3 College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, PR China.
  • 4 College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Maternity and Child Health Hospital, Fuzhou 350001, PR China.
  • 5 Department of Pediatrics, Fujian Children's Hospital(Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, PR China.
  • 6 Pediatric Intensive Care Unit, The Affiliated Hospital(Group) of Putian University, Putian 351100, PR China. Electronic address: 57839649@qq.com.
  • 7 Department of Pediatrics, Fujian Children's Hospital(Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, PR China; College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Maternity and Child Health Hospital, Fuzhou 350001, PR China. Electronic address: Liugh1962815@hotmail.com.
PMID: 39094903 DOI: 10.1016/j.yexcr.2024.114182
Abstract

Kawasaki disease (KD) is a systemic vasculitis with an unknown cause that primarily affects children. The objective of this study was to explore the function and underlying mechanism of Mitophagy in Mycoplasma pneumoniae (MP)-induced KD. To create MP-induced KD models, Human coronary endothelial cells (HCAECs) and DBA/2 mice were employed and treated with Mp-Lipid-associated membrane proteins （LAMPs）. Lactate Dehydrogenase (LDH) levels were tested to determine cellular damage or death. The inflammatory cytokines tumor necrosis factor (TNF)--α and interleukin (IL)-6 were measured using the Enzyme-Linked Immunosorbent Assay (ELISA) method. RT-qPCR and Western blotting were used to determine the expression of Intercellular Adhesion Molecule(ICAM)-1, vascular cell adhesion molecule (VCAM)-1, inducible nitric oxide synthase(iNOS), LC3, p62, PINK1(a mitochondrial serine/threonine-protein kinase), and PARKIN(a cytosolic E3-ubiquitin Ligase). The adenosine triphosphate （ATP）, Reactive Oxygen Species （ROS）, and mitochondrial membrane potential（MMP） levels were measured to determine mitochondrial function. Mitophagy was investigated using immunofluorescence and a Mitophagy detection test. Autophagosome and mitochondrial morphology were examined using transmission electron microscopy. To identify inflammatory cell infiltration, hematoxylin and eosin staining was utilized. Mp-LAMPs increased the levels of TNF-α, IL-6, ICAM-1, VCAM-1, and iNOS in an HCAEC cell model, along with LDH release. After Mp-LAMPs exposure, there was a rise in LC3 and a reduction in p62. Meanwhile, the expression of PINK1 and Parkin was increased. Cyclosporin A dramatically increased ATP synthesis and MMP in HCAEC cells treated with Mp-LAMPs, while suppressing ROS generation, demonstrating excessive mitophagy-related mitochondrial dysfunction. Additionally, neither body weight nor artery tissue were affected due to PINK1 and Parkin suppression Cyclosporin A in Mp-LAMPs-treated mice. These findings indicated that PINK1/Parkin-mediated Mitophagy inhibition may be a therapeutic target for MP-induced KD.

Keywords

Kawasaki disease; Mitophagy; Mycoplasma pneumoniae; PINK1; Parkin.

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