3’UTR shortening of HAS2 promotes hyaluronan hyper-synthesis and bioenergetic dysfunction in pulmonary hypertension
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GRAPHICAL ABSTRACT
Subject Codes
Pulmonary hypertension
Vascular biology
Hyaluronan
extracellular matrix
metabolism
smooth muscle cell
RNA processing deficiency
hypoxia
Nonstandard Abbreviations and Acronyms
3PO
3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one
3’UTR
3’ untranslated region
4MU
4-methylumbelliferone (hyaluronan synthase inhibitor)
APA
alternative polyadenylation
BrdU
5-bromo-2′-deoxyuridine
CCCP
carbonyl cyanide m-chlorophenyl hydrazone
CFIm
cleavage factor 1m, mammalian
dPAS
distal poly-(A) signal
ECAR:
extracellular acidification rate (index of glycolysis)
ECM:
extracellular matrix
FCCP
carbonyl cyanide-4-(trifluoromethyoxy)phenylhydrazone
HA
hyaluronan
HABP
HA binding protein
HMWHA
high molecular weight HA (> 1000 kilodaltons)
HAS
HA synthase
HYAL
hyaluronidase
HYP
hypoxia
HPASMCs
human pulmonary artery smooth muscle cells
IP
intraperitoneal
IPAH
idiopathic pulmonary arterial hypertension
KO
knockout
MOI
multiplicity of infection
NOR
normoxia
NUDT21
nudix hydrolase 21
Oligo
oligomycin
OCR
oxygen consumption rate (index of mitochondrial respiration)
PA
pulmonary artery
PDGF-BB
platelet-derived growth factor-BB
PH
pulmonary hypertension
RT-qPCR
quantitative real-time PCR
R/A
rotenone/antimycin A
RV
right ventricle
RVSP
RV systolic pressure
RV/(LV+S)
right ventricle: left ventricle + septum weight ratio (an index of RVH)
α-SMA
alpha smooth muscle actin
SMC
smooth muscle cell
SMC-HAS2+
SMC-targeted HAS2 transgene overexpressing mouse
SMC-HAS2KO
SMC-targeted HAS2 deletion mouse
siRNA
small interfering RNA
SU
Sugen5416 (vascular endothelial growth factor receptor antagonist)
SU-HYP
SU combined with hypoxia (10% O2)
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© 2022 The Authors. Published by Elsevier B.V.