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Alpha-1 Antitrypsin-Induced Endoplasmic Reticulum Stress Promotes Invasion by Extravillous Trophoblasts
- Source :
- International Journal of Molecular Sciences, Vol 22, Iss 3683, p 3683 (2021), International Journal of Molecular Sciences, Volume 22, Issue 7
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Alpha-1 antitrypsin (A1AT) is a glycoprotein that has been shown to protect tissues from proteolytic damage under various inflammatory conditions. Several studies show that A1AT may be associated with pre-eclampsia. However, the role of A1AT expression in placental physiology is not fully understood. In the present study, we aim to characterize the expression and function of placental A1AT. A1AT knockdown is found to reduce the expression of the serine protease HTRA1 in a trophoblast cell line. In addition, A1AT overexpression (A1AT-OE) increases the expression of HTRA1, IL6, CXCL8, and several markers of endoplasmic reticulum (ER) stress. Treatment with tunicamycin or thapsigargin, which induces ER stress, increases HTRA1 expression. Furthermore, immunohistochemistry reveals that HTRA1 is expressed in trophoblasts and the endometrial decidual cells of human placentas. An invasion assay shows that A1AT and HTRA1 stimulate cell invasion, but treatment with the ER stress inhibitors reduces the expression of HTRA1 and ER stress markers and prevents cell invasion in A1AT-OE trophoblasts. These results suggest that endogenous A1AT regulates inflammatory cytokine expression and HTRA1-induced trophoblast invasion via the induction of ER stress. It is concluded that an imbalance in the functional link between A1AT and ER stress at the maternal–fetal interface might cause abnormal placental development.
- Subjects :
- 0301 basic medicine
Thapsigargin
Catalysis
Article
Cell Line
Inorganic Chemistry
lcsh:Chemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Pre-Eclampsia
Gentamicin protection assay
Pregnancy
medicine
Humans
Decidual cells
Physical and Theoretical Chemistry
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
Inflammation
Gene knockdown
030219 obstetrics & reproductive medicine
Chemistry
Endoplasmic reticulum
Organic Chemistry
Trophoblast
General Medicine
Tunicamycin
cell invasion
eye diseases
Trophoblasts
Computer Science Applications
Cell biology
high-temperature requirement A serine peptidase 1
030104 developmental biology
medicine.anatomical_structure
lcsh:Biology (General)
lcsh:QD1-999
alpha 1-Antitrypsin
Unfolded Protein Response
Unfolded protein response
endoplasmic reticulum stress
Female
alpha-1 antitrypsin
Biomarkers
extravillous trophoblast
Subjects
Details
- Language :
- English
- ISSN :
- 16616596 and 14220067
- Volume :
- 22
- Issue :
- 3683
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....574461dad3253378a1bab50ff0cccf2c