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2015 ; 2015
(ä): 481493
Nephropedia Template TP
Mirzapoiazova T
; Lennon FE
; Mambetsariev B
; Allen M
; Riehm J
; Poroyko VA
; Singleton PA
Int J Cell Biol
2015[]; 2015
(ä): 481493
PMID26447809
show ga
Defects in vascular integrity are an initiating factor in several disease
processes. We have previously reported that high molecular weight hyaluronan
(HMW-HA), a major glycosaminoglycan in the body, promotes rapid signal
transduction in human pulmonary microvascular endothelial cells (HPMVEC) leading
to barrier enhancement. In contrast, low molecular weight hyaluronan (LMW-HA),
produced in disease states by hyaluronidases and reactive oxygen species (ROS),
induces HPMVEC barrier disruption. However, the mechanism(s) of sustained barrier
regulation by HA are poorly defined. Our results indicate that long-term (6-24
hours) exposure of HMW-HA induced release of a novel type of extracellular
vesicle from HLMVEC called enlargeosomes (characterized by AHNAK expression)
while LMW-HA long-term exposure promoted release of exosomes (characterized by
CD9, CD63, and CD81 expression). These effects were blocked by inhibiting
caveolin-enriched microdomain (CEM) formation. Further, inhibiting enlargeosome
release by annexin II siRNA attenuated the sustained barrier enhancing effects of
HMW-HA. Finally, exposure of isolated enlargeosomes to HPMVEC monolayers
generated barrier enhancement while exosomes led to barrier disruption. Taken
together, these results suggest that differential release of extracellular
vesicles from CEM modulate the sustained HPMVEC barrier regulation by HMW-HA and
LMW-HA. HMW-HA-induced specialized enlargeosomes can be a potential therapeutic
strategy for diseases involving impaired vascular integrity.