Knockdown of the long noncoding RNA VSIG2-1:1 promotes the angiogenic ability of human pulmonary microvascular endothelial cells by activating the VEGF/PI3K/AKT pathway

Xiaoya Hu; Yihui Zheng; Mingchu Fang; Zhongjie Liang; Chao Wen; Jing Lin; Zhenlang Lin; Shangqin Chen

doi:10.1186/s12931-024-03039-y

Knockdown of the long noncoding RNA VSIG2-1:1 promotes the angiogenic ability of human pulmonary microvascular endothelial cells by activating the VEGF/PI3K/AKT pathway

Respir Res. 2024 Nov 20;25(1):412. doi: 10.1186/s12931-024-03039-y.

Authors

Xiaoya Hu¹, Yihui Zheng^{1

2

3}, Mingchu Fang^{1

2

3}, Zhongjie Liang¹, Chao Wen¹, Jing Lin^{1

4}, Zhenlang Lin^{5

6

7}, Shangqin Chen⁸

Affiliations

¹ Wenzhou Key Laboratory of Perinatal Medicine, Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, China.
² Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325000, Zhejiang Province, China.
³ Zhejiang Provincial Clinical Research Center for Pediatric Disease, Wenzhou, 325000, Zhejiang Province, China.
⁴ Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
⁵ Wenzhou Key Laboratory of Perinatal Medicine, Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, China. linzhenlang@hotmail.com.
⁶ Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325000, Zhejiang Province, China. linzhenlang@hotmail.com.
⁷ Zhejiang Provincial Clinical Research Center for Pediatric Disease, Wenzhou, 325000, Zhejiang Province, China. linzhenlang@hotmail.com.
⁸ Wenzhou Key Laboratory of Perinatal Medicine, Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, China. chensq5725@163.com.

PMID: 39568008
DOI: 10.1186/s12931-024-03039-y

Abstract

Background: Abnormal pulmonary vascular development poses significant clinical challenges for infants with bronchopulmonary dysplasia (BPD). Although numerous factors have been suggested to control the development of pulmonary blood vessels, the mechanisms underlying the role of long noncoding RNAs (lncRNAs) in this process remain unclear.

Methods: A lncRNA array was used to measure the differential expression of lncRNAs in premature infants with and without BPD. The expression of lncRNA-VSIG2-1:1 in patients with BPD and hyperoxia-induced human pulmonary microvascular endothelial cells (HPMECs) was assessed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Fluorescence in situ hybridization (FISH) assay was performed to detect the subcellular localization of lncRNA-VSIG2-1:1. Pulmonary microvascular endothelial cells were stably transfected with adenoviral vectors to silence or overexpress lncRNA-VSIG2-1:1. The effects of lncRNA-VSIG2-1:1 on the proliferation, migration, and tube formation abilities of HPMECs subjected to hyperoxia were examined by performing Cell Counting Kit-8 (CCK-8), cell migration, and tubule formation assays. RNA sequencing (RNA-seq) was performed to determine the correlation between lncRNA-VSIG2-1:1 and phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT). The protein levels of vascular endothelial growth factor (VEGF), p-PI3K, PI3K, p-AKT, and AKT were determined using western blotting.

Results: The expression of lncRNA-VSIG2-1:1 was upregulated in patients with BPD and hyperoxia-treated HPMECs. Inhibiting lncRNA-VSIG2-1:1 expression promoted the proliferation, migration, and tube-formation abilities of HPMECs, while significantly increasing VEGF, p-PI3K, and p-AKT levels.

Conclusion: Our findings reveal that the suppression of lncRNA-VSIG2-1:1 expression stimulates angiogenesis in vitro by inducing the initiation of the VEGF/PI3K/AKT signaling pathway. This observation may aid the development of novel therapeutic targets for treating BPD.

Keywords: Angiogenesis; Bronchopulmonary dysplasia; Long noncoding RNA; Pulmonary microvascular endothelial cells; VEGF/PI3K/AKT pathway.

Abstract

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