Stress signaler p38 mitogen-activated kinase activation: a cause for concern?

Author:

Radnaa Enkhtuya1,Richardson Lauren1,Goldman Brett1,Burks Jared K.2,Baljinnyam Tuvshintugs3,Vora Natasha1,Zhang Hui-juan4,Bonney Elizabeth A.5,Han Arum6,Menon Ramkumar1

Affiliation:

1. 1Division of Basic and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas, U.S.A.

2. 2Flow Cytometry and Cellular Imaging Core Facility, Department of Leukemia, M.D. Anderson Cancer Center, Texas, U.S.A. 77030

3. 3Department of Pharmacology and Toxicology, The University of Texas Medical Branch at Galveston, Galveston, Texas, U.S.A. 77555

4. 4Department of Pathology, The International Peace Maternity and Child Health Hospital, University School of Medicine, Shanghai, China. 200030

5. 5Department of Obstetrics and Gynecology, The University of Vermont, Burlington, VT, U.S.A. 05405ghout all figures, the following notations were

6. 6Department of Electrical and Computer Engineering, Department of Biomedical Engineering, Texas A&M University, College Station, Texas, U.S.A. 77843

Abstract

Abstract Oxidative stress (OS) induced activation of p38 mitogen-activated kinase (MAPK) and cell fate from p38 signaling was tested using the human fetal membrane’s amnion epithelial cells (AEC). We created p38 KO AEC using the CRISPR/Cas9 approach and tested cell fate in response to OS on an AEC-free fetal membrane extracellular matrix (ECM). Screening using image CyTOF indicated OS causing epithelial–mesenchymal transition (EMT). Further testing revealed p38 deficiency prevented AEC senescence, EMT, cell migration, and inflammation. To functionally validate in vitro findings, fetal membrane-specific conditional KO (cKO) mice were developed by injecting Cre-recombinase encoded exosomes intra-amniotically into p38αloxP/loxP mice. Amnion membranes from p38 cKO mice had reduced senescence, EMT, and increased anti-inflammatory IL-10 compared with WT animals. Our study suggested that overwhelming activation of p38 in response to OS inducing risk exposures can have an adverse impact on cells, cause cell invasion, inflammation, and ECM degradation detrimental to tissue homeostasis.

Publisher

Portland Press Ltd.

Subject

General Medicine

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