Your browser doesn't support javascript.
loading
N-Acetyl-Seryl-Asparyl-Lysyl-Proline regulates lung renin angiotensin system to inhibit epithelial-mesenchymal transition in silicotic mice.
Li, Shumin; Li, Yaqian; Zhang, Yi; Li, Shifeng; Zhang, Min; Jin, Fuyu; Wei, Zhongqiu; Yang, Yi; Gao, Xuemin; Mao, Na; Ge, Xingchen; Xu, Hong; Yang, Fang.
Afiliación
  • Li S; School of Public Health, North China University of Science and Technology, Tangshan 063210, Hebei, China; School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, Hebei, China.
  • Li Y; School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, Hebei, China; Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan 063210, Hebei, China.
  • Zhang Y; School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, Hebei, China.
  • Li S; School of Public Health, North China University of Science and Technology, Tangshan 063210, Hebei, China; Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan 063210, Hebei, China.
  • Zhang M; Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan 063210, Hebei, China.
  • Jin F; School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, Hebei, China; Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan 063210, Hebei, China.
  • Wei Z; School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, Hebei, China.
  • Yang Y; School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, Hebei, China.
  • Gao X; Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan 063210, Hebei, China.
  • Mao N; School of Public Health, North China University of Science and Technology, Tangshan 063210, Hebei, China.
  • Ge X; Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan 063210, Hebei, China.
  • Xu H; School of Public Health, North China University of Science and Technology, Tangshan 063210, Hebei, China; Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan 063210, Hebei, China.
  • Yang F; School of Public Health, North China University of Science and Technology, Tangshan 063210, Hebei, China; Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan 063210, Hebei, China. Electronic address: fangyang@ncst.edu.cn.
Toxicol Appl Pharmacol ; 408: 115255, 2020 12 01.
Article en En | MEDLINE | ID: mdl-33007385
Silicosis is a major public health concern with various contributing factors. The renin-angiotensin system (RAS)is a critical regulator in the pathogenesis of this disease. We focused on two key RAS enzymes, angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2), to elucidate the activation of the ACE-angiotensin II (Ang II)-angiotensin II receptor 1 (AT1) axis and the inhibition of the ACE2-angiotensin-(1-7) [Ang-(1-7)]-Mas receptor axis in C57BL/6mice following SiO2 treatment. Silica exposure caused nodule formation, pulmonary interstitial fibrosis, epithelial-mesenchymal transition (EMT), abnormal deposition of extracellular matrix, and impaired lung function in mice. These effects were attenuated by the inhibition of ACE (captopril), blockade of the AT1(losartan), or systemic knockdown of the Ace gene. These effects were exacerbated by the inhibition of ACE2 (MLN-4760), blockade of the Mas (A779), or knockdown of the Ace2 gene. N-Acetyl-Seryl-Asparyl-Lysyl-Proline (Ac-SDKP), an anti-fibrotic peptide, ameliorated the silica-exposure-induced pathological changes by targeting the RAS system by activating the protective ACE2-Ang-(1-7)-Mas axis and inhibiting the deleterious ACE-Ang II-AT1 axis, thereby exerting a protective effect. This was confirmed in mouse lung type II epithelial cells (MLE-12) pretreated with Ang II and/or gene silencing separately targeting Ace and Ace2.The effects of Ac-SDKP were similar to those produced by Ace gene silencing and were partly attenuated by Ace2 deficiency. These findings suggested that RAS plays critical roles in the pathomechanism of silicosis fibrosis and that Ac-SDKP regulates lung RAS to inhibit EMT in silicotic mice and MLE-12 cells.
Asunto(s)
Palabras clave
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: Oligopéptidos / Sistema Renina-Angiotensina / Silicosis / Transición Epitelial-Mesenquimal / Pulmón Límite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
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: Oligopéptidos / Sistema Renina-Angiotensina / Silicosis / Transición Epitelial-Mesenquimal / Pulmón Límite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos