Hyperglycemia is a causative factor in the pathogenesis of respiratory diseases, known to induce fibrosis and inflammation in the lung. However, little attention has been paid to genes related to hyperglycemic-induced lung alterations and stem cell applications for therapeutic use. In this study, our microarray data revealed significantly increased levels of junctional adhesion molecule 2 (JAM2) in the high glucose (HG)-induced transcriptional profile in human perivascular cells (hPVCs). The elevated level of JAM2 in HG-treated hPVCs was transcriptionally and epigenetically reversible when HG treatment was removed. We further investigated the expression of JAM2 using in vivo and in vitro hyperglycemic models. Our results showed significant upregulation of JAM2 in the lungs of streptozotocin (STZ)-induced diabetic mice, which was greatly suppressed by the administration of conditioned medium obtained from human mesenchymal stem cell cultures. Furthermore, JAM2 was found to be significantly upregulated in human pluripotent stem cell-derived multicellular alveolar organoids by exposure to HG. Our results suggest that JAM2 may play an important role in STZ-induced lung alterations and could be a potential indicator for predicting the therapeutic effects of stem cells and drugs in diabetic lung complications.
Gestational diabetes mellitus (GDM), one of the common metabolic disorders of pregnancy, leads to functional alterations in various cells including stem cells as well as some abnormalities in fetal development. Perivascular stem cells (PVCs) have gained more attention in recent years, for the treatment of various diseases. However, the effect of GDM on PVC function has not been investigated. In our study, we isolated PVCs from umbilical cord of normal pregnant women and GDM patients and compared their phenotypes and function. There is no significant difference in phenotypic expression, response to bFGF exposure and adipogenic differentiation capacity between normal (N)-PVCs and GDM-PVCs. However, when compared with N-PVCs, early passage GDM-PVCs displayed decreased initial rates of cell yield and proliferation as well as a reduced ability to promote wound closure. These results suggest that maternal metabolic dysregulation during gestation can alter the function of endogenous multipotent stem cells, which may impact their therapeutic effectiveness.
Potassium channels, the largest group of pore proteins, selectively regulate the
flow of potassium (K+) ions across cell membranes. The activity and
expression of K+ channels are critical for the maintenance of normal
functions in vessels and neurons, and for the regulation of cell differentiation
and maturation. However, their role and expression in stem cells have been
poorly understood. In this study, we isolated perivascular stem cells (PVCs)
from human umbilical cords and investigated the expression patterns of
big-conductance Ca2+-activated K+ (BKCa) and
voltage-dependent K+ (Kv) channels using the reverse
transcription polymerase chain reaction. We also examined the effect of high
glucose (HG, 25 mM) on expression levels of BKCa and Kv
channels in PVCs. KCa1.1, KCaβ3,
Kv1.3, Kv3.2, and Kv6.1 were detected in
undifferentiated PVCs. In addition, HG treatment increased the amounts of
BKCaβ3a, BKCaβ4,
Kv1.3, Kv1.6, and Kv6.1 transcripts. These
results suggested that ion channels may have important functions in the growth
and differentiation of PVCs, which could be influenced by HG exposure.
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