Biology subjects

Sturgill, J.

Publications and source records attributed to Sturgill, J..

3 recordsLinked to original sources

bioRxiv2024

Mitochondria-Associated Membranes Are Not Altered In Immune Cells In T2D

Metabolism research is increasingly recognizing the contributions of organelle crosstalk to metabolic regulation. Mitochondria-associated membranes (MAMs), which are structures connecting the mitochondria and endoplasmic reticulum (ER), are critical in a myriad of cellular functions linked to cellular metabolism. MAMs control calcium signaling, mitochondrial transport, redox balance, protein folding/degradation, and in some studies, metabolic health. The possibility that MAMs drive changes in cellular function in individuals with Type 2 Diabetes (T2D) is controversial. Although disruptions in MAMs that change the distance between the mitochondria and ER, MAM protein composition, or disrupt downstream signaling, can perpetuate inflammation, one key trait of T2D. However, the full scope of this structures role in immune cell health and thus T2D-associated inflammation remains unknown. We show that human immune cell MAM proteins and their associated functions are not altered by T2D and thus unlikely to contribute to metaflammation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/586170v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1a281f1org.highwire.dtl.DTLVardef@1025corg.highwire.dtl.DTLVardef@42259eorg.highwire.dtl.DTLVardef@b3bbb1_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2021

SARS-CoV-2 Spike Protein Regulation of Angiotensin Converting Enzyme 2 and Tissue Renin-Angiotensin Systems: Influence of Biologic Sex

Angiotensin converting enzyme 2 (ACE2) is an enzyme that limits activity of the renin-angiotensin system (RAS) and also serves as a receptor for the SARS-CoV-2 Spike (S) protein. Binding of S protein to ACE2 causes internalization which activates local RAS. ACE2 is on the X chromosome and its expression is regulated by sex hormones. In this study, we defined ACE2 mRNA abundance and examined effects of S protein on ACE2 activity and/or angiotensin II (AngII) levels in pivotal tissues (lung, adipose) from male and female mice. In lung, ACE2 mRNA abundance was reduced following gonadectomy (GDX) of male and female mice and was higher in XX than XY mice of the Four Core Genotypes (FCG). Reductions in lung ACE2 mRNA abundance by GDX occurred in XX, but not XY FCG female mice. Lung mRNA abundance of ADAM17 and TMPRSS2, enzymes that shed cell surface ACE2 and facilitate viral cell entry, was reduced by GDX in male but not female mice. For comparison, adipose ACE2 mRNA abundance was higher in female than male mice and higher in XX than XY FCG mice. Adipose ADAM17 mRNA abundance was increased by GDX of male and female mice. S protein reduced ACE2 activity in alveolar type II epithelial cells and 3T3-L1 adipocytes. Administration of S protein to male and female mice increased lung AngII levels and decreased adipose ACE2 activity in male but not female mice. These results demonstrate that sex differences in ACE2 expression levels may impact local RAS following S protein exposures.

physiology↗

bioRxiv2019

Mast cells are mediators of fibrosis and effector cell recruitment in dermal chronic graft-versus-host disease

Allogeneic hematopoietic stem cell transplant (allo-HSCT) is often used to treat acute leukemia or defects of hematopoiesis. Its widespread use is hampered by graft-versus-host disease (GVHD), which has high morbidity and mortality in both acute and chronic subtypes. Chronic GVHD (cGVHD) occurs most frequently in skin and often is characterized by pathogenic fibrosis. Mast cells (MCs) are known to be involved in the pathogenesis of other fibrotic diseases. In a murine model of cGVHD after allo-HSCT, C57BL/6J recipients of allogeneic LP/J donor cells develop sclerodermatous dermal cGVHD which is significantly decreased in mast cell-deficient B6.Cg-KitW-sh/HNihrJaeBsmGlliJ recipients. MCs survive conditioning and are associated with fibrosis, chemokine production, and recruitment of GVHD effector cells to the skin. Chemokine production by MCs is blocked by drugs used to treat cGVHD. The importance of MCs in skin cGVHD is mirrored by increased MCs in the skin of patients with dermal cGVHD. We show for the first time a role for MCs in skin cGVHD that may be targetable for preventive and therapeutic intervention in this disease.

immunology↗