Table 1.

Role of RBPS in pulmonary hypertension.

RBP	Experimental System	Target mRNA(s)	RNA Metabolism Alteration	Phenotype/Function	Reference
SFPQ	Pulmonary artery adventitial fibroblasts isolated from rat	CD40	Transcription	Reduced levels of RBP SFPQ promote activation of pulmonary artery adventitial fibroblasts via activating CD40 transcription	[63]
PTBP1	Human patient samples; human and bovine pulmonary artery fibroblasts; human PAECs; human BOECs	PKM (PKM1 and PKM2)	Splicing	Increased levels of splicing repressor PTBP1 inhibit the usage of exon 9 of PKM pre-mRNA, resulting in increased generation of PKM2 and alteration of phenotypes of PH vascular and circulating cells.	[64,65,66]
SRSF2	Lymphocytes (CLs) from BMPR2 mutation-positive HPAH patients and unaffected carriers; human pulmonary microvascular endothelial cells (PMVECs)	BMPR2 (isoform B and A)	Splicing	Reduced levels of splicing activator SRSF2 increase the levels of non-functional BMPR2 B isoform in PH cells from affected BMPR2 mutation carriers (who develop PH), providing an explanation of the reduced penetrance among BMPR2 heterozygous mutation carriers.	[67]
HF related splicing factor(s)	Peripheral blood mononuclear cells (PBMCs) isolated from Patients with Group 1 PAH and Controls	SCN5a	Splicing	Increased levels of RBP (might be RBM25 and LUC7L3) promote the generation of non-functional splicing variant of SCN5a in heart failure and PH	[68]
ZFC3H1	PASMCs from patients with PAH	BRD4 and HIF1α	Stability	As a binding partner of Celastramycin, ZFC3H1 mediates inhibition of BRD4 and HIF-1a by Celastramycin treatment through regulating the degradation of nuclear RNAs in PASMCs	[69]
HuR	Pulmonary arteries of hypoxic mice PH model	sGC-α1	Stability	Increased translocation of HuR protein from cytoplasm to nucleus de-stabilizes sGC-a1 mRNA in mouse pulmonary arteries, thus reducing NO/sGC signaling in response to short-term hypoxia	[70]
TLR3	PAECs, Pulmonary arteries and lung tissue of patients with PH; rat endothelial cells; Chronic hypoxia and SU5416 TLR3−/− and TLR3+/+ mice; chronic hypoxia/SU5416 rats	IL-10 CXCL10 (IP10)	Transcription	TLR3 expression is significantly reduced in PAECs, remodeled arteries, and lung tissue of patients with PH. TLR3 activation by a synthetic ligand of double-stranded RNA (poly[I:C]), ameliorated established experimental PH in rat models.	[71,72]