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circNFXL1 Modulates the Kv2.1 Channel Function in Hypoxic Human Pulmonary Artery Smooth Muscle Cells via Sponging miR-29b-2-5p as a Competitive Endogenous RNA.
Li, Shan-Shan; Liang, Shuang; Li, Lu; Yang, Houzhi; Long, Yao; Zhuo, Donghai; Chen, Xu; Jin, Xin.
Afiliação
  • Li SS; School of Medicine, Nankai University, Tianjin, China.
  • Liang S; Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China.
  • Li L; School of Medicine, Nankai University, Tianjin, China.
  • Yang H; Tianjin Medical University, Tianjin, China; and.
  • Long Y; School of Medicine, Nankai University, Tianjin, China.
  • Zhuo D; School of Medicine, Nankai University, Tianjin, China.
  • Chen X; School of Medicine, Nankai University, Tianjin, China.
  • Jin X; Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China.
J Cardiovasc Pharmacol ; 81(4): 292-299, 2023 04 01.
Article em En | MEDLINE | ID: mdl-36651941
ABSTRACT: Pulmonary arterial hypertension is characterized by abnormal pulmonary vasoconstriction and vascular remodeling caused by the dysregulation of K + channels in PA smooth muscle cells (PASMCs). However, how the K + channels are dysregulated is still unclear. Circular RNAs (circRNAs) are noncoding RNAs with a closed-loop structure capable of sponging microRNAs (miRs), thus regulating gene expression at the post-transcriptional level. Our previous studies have demonstrated the importance of one novel circRNA (hsa_circNFXL1_009, circNFXL1) in pulmonary arterial hypertension patients, playing as a critical regulator for K + channel activation in hypoxic human PASMCs (hPASMCs). Here, we explore the mechanisms underlying circNFXL1-regulated K + channel expression and functions in hypoxic hPASMCs. In cultured hPASMCs, the reduction of Kv current induced by hypoxia was significantly recovered by delivering exogenous circNFXL1. Moreover, luciferase, quantitative reverse transcription-quantitative polymerase chain reaction, western blot, and mutagenesis studies confirmed that circNFXL1 reversed hypoxia-induced inhibitory effects on the Kv2.1 channel via sponging hsa-miR-29b-2-5p (miR-29b-2). Furthermore, we found that circNFXL1 reversed the miR-29b-induced Kv2.1 channel dysfunction at the whole-cell and single-channel level in HEK cells using a patch-clamp. Finally, calcium imaging revealed that hypoxia also triggered a substantial rise in the cytosolic calcium concentration ([Ca2 + ]cyt) in hPASMCs, and this hypoxia-induced elevation of [Ca2 + ]cyt was reduced by circNFXL1 through miR-29b-2. These data suggested that circNFXL1-mediated regulation of the Kv2.1 channel activation and the related intracellular calcium concentration may contribute to the effects of hypoxic pulmonary vasoconstriction.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: MicroRNAs / Hipertensão Arterial Pulmonar Limite: Humans Idioma: En Revista: J Cardiovasc Pharmacol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: MicroRNAs / Hipertensão Arterial Pulmonar Limite: Humans Idioma: En Revista: J Cardiovasc Pharmacol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China