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Nupr1-mediated vascular smooth muscle cell phenotype transformation involved in methamphetamine induces pulmonary hypertension.
Zhou, Jie; Guo, Dan; Xu, Zhen-Zhen; Liao, Jia-Shun; Li, Xiao-Ting; Duan, Ke; Chen, Shi-You; Xie, Wei-Bing.
Afiliación
  • Zhou J; Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China.
  • Guo D; Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China.
  • Xu ZZ; Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China.
  • Liao JS; Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China.
  • Li XT; Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China.
  • Duan K; Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China.
  • Chen SY; Department of Surgery, Medical Pharmacology & Physiology, University of Missouri, Columbia, MO, 65212, USA.
  • Xie WB; Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China. xwb@smu.edu.cn.
Cell Biol Toxicol ; 40(1): 13, 2024 02 13.
Article en En | MEDLINE | ID: mdl-38347241
ABSTRACT

AIMS:

Nuclear protein 1 (Nupr1) is a multifunctional stress-induced protein involved in the regulation of tumorigenesis, apoptosis, and autophagy. However, its role in pulmonary hypertension (PH) after METH exposure remains unexplored. In this study, we aimed to investigate whether METH can induce PH and describe the role and mechanism of Nupr1 in the development of PH. METHODS AND

RESULTS:

Mice were made to induce pulmonary hypertension (PH) upon chronic intermittent treatment with METH. Their right ventricular systolic pressure (RVSP) was measured to assess pulmonary artery pressure. Pulmonary artery morphometry was determined by H&E staining and Masson staining. Nupr1 expression and function were detected in human lungs, mice lungs exposed to METH, and cultured pulmonary arterial smooth muscle cells (PASMCs) with METH treatment. Our results showed that chronic intermittent METH treatment successfully induced PH in mice. Nupr1 expression was increased in the cultured PASMCs, pulmonary arterial media from METH-exposed mice, and METH-ingested human specimens compared with control. Elevated Nupr1 expression promoted PASMC phenotype change from contractile to synthetic, which triggered pulmonary artery remodeling and resulted in PH formation. Mechanistically, Nupr1 mediated the opening of store-operated calcium entry (SOCE) by activating the expression of STIM1, thereby promoting Ca2+ influx and inducing phenotypic conversion of PASMCs.

CONCLUSIONS:

Nupr1 activation could promote Ca2+ influx through STIM1-mediated SOCE opening, which promoted METH-induced pulmonary artery remodeling and led to PH formation. These results suggested that Nupr1 played an important role in METH-induced PH and might be a potential target for METH-related PH therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hipertensión Pulmonar / Metanfetamina Límite: Animals / Humans Idioma: En Revista: Cell Biol Toxicol Asunto de la revista: TOXICOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hipertensión Pulmonar / Metanfetamina Límite: Animals / Humans Idioma: En Revista: Cell Biol Toxicol Asunto de la revista: TOXICOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Suiza