The Autophagy Protein Pacer Positively Regulates the Therapeutic Potential of Mesenchymal Stem Cells in a Mouse Model of DSS-Induced Colitis
Journal
Cells
ISSN
2073-4409
Date Issued
2022
Author(s)
Cristian A. Bergmann
Sebastian Beltran
Ana Maria Vega-Letter
Paola Murgas
Maria Fernanda Hernandez
Laura Gomez
Luis Labrador
Bastián I. Cortés
Cristian Poblete
Cristobal Quijada
Ute Woehlbier
Patricio A. Manque
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>Mesenchymal stem cells (MSC) have emerged as a promising tool to treat inflammatory diseases, such as inflammatory bowel disease (IBD), due to their immunoregulatory properties. Frequently, IBD is modeled in mice by using dextran sulfate sodium (DSS)-induced colitis. Recently, the modulation of autophagy in MSC has been suggested as a novel strategy to improve MSC-based immunotherapy. Hence, we investigated a possible role of Pacer, a novel autophagy enhancer, in regulating the immunosuppressive function of MSC in the context of DSS-induced colitis. We found that Pacer is upregulated upon stimulation with the pro-inflammatory cytokine TNFα, the main cytokine released in the inflammatory environment of IBD. By modulating Pacer expression in MSC, we found that Pacer plays an important role in regulating the autophagy pathway in this cell type in response to TNFα stimulation, as well as in regulating the immunosuppressive ability of MSC toward T-cell proliferation. Furthermore, increased expression of Pacer in MSC enhanced their ability to ameliorate the symptoms of DSS-induced colitis in mice. Our results support previous findings that autophagy regulates the therapeutic potential of MSC and suggest that the augmentation of autophagic capacity in MSC by increasing Pacer levels may have therapeutic implications for IBD.</jats:p>
Subjects
autophagy
;
colitis
;
inflammatory bowel disease
;
kiaa0226l
;
mesenchymal stem cells
;
pacer
;
rubcnl
;
therapy
;
animals
;
autophagy
;
colitis
;
cytokines
;
dextran sulfate
;
disease models, animal
;
inflammatory bowel diseases
;
mesenchymal stem cell transplantation
;
mesenchymal stem cells
;
mice
;
tumor necrosis factor-alpha
;
autophagy protein pacer
;
autophagy related protein
;
complementary dna
;
cytokine
;
interleukin 6
;
messenger rna
;
small interfering rna
;
transforming growth factor beta1
;
tumor necrosis factor
;
unclassified drug
;
cytokine
;
dextran sulfate
;
tumor necrosis factor
;
animal experiment
;
animal model
;
article
;
autophagy (cellular)
;
autophagy assay
;
body weight loss
;
cell assay
;
cell culture
;
cell infiltration
;
cell proliferation
;
cell proliferation assay
;
clinical disease activity index
;
dextran sulfate sodium-induced colitis
;
diarrhea
;
female
;
goblet cell
;
hek293t cell line
;
histopathology
;
immunoblotting
;
immunohistochemistry
;
immunosuppressive treatment
;
inflammatory bowel disease
;
leukocyte
;
mesenchymal stem cell
;
mouse
;
nonhuman
;
protein expression
;
rectum hemorrhage
;
reverse transcription polymerase chain reaction
;
t lymphocyte
;
upregulation
;
animal
;
autophagy
;
colitis
;
disease model
;
inflammatory bowel disease
;
mesenchymal stem cell transplantation
;
metabolism
;
procedures