1. Academic Validation
  2. TFAM-Mediated mitochondrial transfer of MSCs improved the permeability barrier in sepsis-associated acute lung injury

TFAM-Mediated mitochondrial transfer of MSCs improved the permeability barrier in sepsis-associated acute lung injury

  • Apoptosis. 2023 Apr 15. doi: 10.1007/s10495-023-01847-z.
Feng Zhang 1 Xinglong Zheng 1 Fengzhi Zhao 1 Longzhu Li 1 Yinlong Ren 1 Lijun Li 1 Haiyan Huang 1 Haiyan Yin 2
Affiliations

Affiliations

  • 1 Department of Intensive Care Unit, the First Affiliated Hospital of Jinan University, No.613, West Huangpu Avenue, Guangzhou, 510630, Guangdong, China.
  • 2 Department of Intensive Care Unit, the First Affiliated Hospital of Jinan University, No.613, West Huangpu Avenue, Guangzhou, 510630, Guangdong, China. yinhaiyan1867@126.com.
Abstract

Vascular endothelial cell barrier disruption is a hallmark of sepsis-induced acute lung injury (ALI). Mesenchymal stem cells (MSCs)-based therapy has been regarded as a promising treatment for repairing injured lungs, and mitochondrial transfer was shown to be important for the therapeutic effects of MSCs. Here we investigated the ability of MSCs to modulate endothelial barrier integrity through mitochondrial transfer in sepsis-induced ALI. We found that mitochondrial transfer from MSCs to LPS-induced PMVECs through forming tunneling nanotubes (TNTs). Due to the inhibition of TNTs (using LAT-A), MSCs-mediated reparation on PMVECs functions, including cell Apoptosis, MMP, ATP generation, TEER level and monolayer permeability of FITC-dextran were greatly inhibited. In addition, silencing of mitochondrial transcription factor A (TFAM) in MSCs could also partly inhibit the TNTs formation and aggravate the LPS-induced mitochondrial dysfunction and permeability barrier in PMVECs. Furthermore, the LPS-induced pulmonary edema and higher pulmonary vascular permeability were alleviated by MSCs while that of lung tissue bounced back after MSCs were pre-incubated by LAT-A and or down-regulation of TFAM. Therefore, we firstly revealed that regulation of TFAM expression in MSCs played a critical role to improve the permeability barrier of PMVECs by TNTs mediating mitochondrial transfer in sepsis-associated ALI. This study provided a new therapeutic strategy for the treatment of sepsis-induced ALI.

Keywords

Mitochondrial transcription factor A; Mitochondrial transfer; Permeability barrier; Sepsis-associated acute lung injury; Tunneling nanotubes.

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