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Decreased gene expression of adrenomedullin receptor in mouse lungs during sepsis
1Department of Anesthesiology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
Abstract:
Plasma concentrations of adrenomedullin (AM) are markedly increased during sepsis, but the role of AM has not been clarified. Coexpression of calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein (RAMP) 2 or 3 have been reported to form the adrenomedullin (AM) specific receptor. We examined the expression of CRLR and RAMP1, 2, and 3 in several tissues from mice in a sepsis model induced by lipopolysaccharide (LPS). High expression of CRLR and RAMP2 mRNA was observed in lungs of normal mice, but it was markedly decreased in endotoxemic mice. It is suggested that the abundant binding sites of AM in lungs are formed by CRLR and RAMP2 in healthy subjects and that their reduction should contribute to the increase of plasma AM concentrations during sepsis. In contrast, LPS treatment markedly increased RAMP3 gene expression in lungs, spleen, and thymus. It is revealed that the distributions of receptor or binding sites of AM are changed in sepsis, and it is suggested that AM plays distinct roles in the clinical course of this syndrome.
Insights
During sepsis, adrenomedullin (AM) levels rise. Researchers found that key AM receptor components (CRLR and RAMP2) decrease in lungs, while RAMP3 increases, altering AM signaling in this condition.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Plasma concentrations of adrenomedullin (AM) increase significantly during sepsis.
- The specific role of AM and its receptor components in sepsis remains unclear.
- Adrenomedullin receptors are formed by coexpression of calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMP) 2 or 3.
Purpose of the Study:
- To investigate the expression of CRLR and RAMPs (1, 2, and 3) in various tissues during a mouse model of sepsis.
- To elucidate the changes in AM receptor distribution and their potential contribution to elevated plasma AM levels in sepsis.
Main Methods:
- Sepsis was induced in mice using lipopolysaccharide (LPS).
- Quantitative analysis of CRLR, RAMP1, RAMP2, and RAMP3 mRNA expression in lung, spleen, and thymus tissues was performed.
- Comparison of gene expression patterns between normal and endotoxemic mice.
Main Results:
- Normal mice exhibited high expression of CRLR and RAMP2 mRNA in lung tissue.
- Endotoxemic mice showed a marked decrease in CRLR and RAMP2 mRNA expression in the lungs.
- LPS treatment significantly increased RAMP3 gene expression in the lungs, spleen, and thymus.
Conclusions:
- The reduction of CRLR and RAMP2 in healthy subjects' lungs may form abundant AM binding sites, and their decrease during sepsis contributes to increased plasma AM.
- Sepsis alters the distribution of AM receptors, with increased RAMP3 expression in multiple tissues.
- These changes suggest that adrenomedullin plays distinct roles in the pathophysiology of sepsis.