Molecular regulation and clinical significance of caveolin-1 methylation in chronic lung diseases

Abstract

Chronic lung diseases represent a largely global burden whose pathogenesis remains largely unknown. Research increasingly suggests that epigenetic modifications, especially DNA methylation, play a mechanistic role in chronic lung diseases. DNA methylation can affect gene expression and induce various diseases. Of the caveolae in plasma membrane of cell, caveolin-1 (Cav-1) is a crucial structural constituent involved in many important life activities. With the increasingly advanced progress of genome-wide methylation sequencing technologies, the important impact of Cav-1 DNA methylation has been discovered. The present review overviews the biological characters, functions, and structure of Cav-1; epigenetic modifications of Cav-1 in health and disease; expression and regulation of Cav-1 DNA methylation in the respiratory system and its significance; as well as clinical potential as disease-specific biomarker and targets for early diagnosis and therapy.

Keywords: caveolae; caveolin-1; chronic lung diseases; epigenetic modification; methylation.

FIGURE 1

The structure of caveolae. Caveolae are a kind of flask‐shaped invaginations in the plasma membrane, including caveolin, cavin (also named polymerase I and transcript release factor (PTRF)), lipids, and so on. Cav‐1 is the major integral membrane protein for the assembly of caveolae. Cav‐1 contains a highly conserved domain named caveolin scaffolding domain (CSD, acids 82‐101). The CSD domain takes part in the interactions with signaling proteins and regulates signal transduction in various cellular processes

FIGURE 2

Cav‐1 in the respiratory system. Caveolae widely exists in many cells of the respiratory system and are involved in various cellular activities. Cav‐1 as the important structural proteins of caveolae is involved in a variety of signaling pathways, and the abnormal expression level of it will lead to the structural and functional dysfunction and induce the occurrence of diseases

FIGURE 3

Two major epigenetics influence in gene expression. There are two major mechanisms involved in epigenetic regulation. One is the DNA methylation, changes on that could influence the gene expression level of gene. The other one is histone modification, which contains phosphorylation, methylation, and acetylation

FIGURE 4

DNA methylation changes in Cav‐1 gene expression. Methylation refers to the process of catalyzing the transfer of methyl groups from active methyl compounds to other compounds. DNA methylation generally occurs at the CpG site of gene promoter region. DNA methylation is an important modification of genes, which could regulate the expression level of genes and is closely related to many diseases. It is one of the crucial researches on epigenetic regulation

FIGURE 5

Epigenetic regulation changes in Cav‐1 gene expression. DNA methylation and histone modification are the two major mechanisms of Cav‐1 gene. Epigenetic regulation changes in Cav‐1 gene could act as diagnosis and prognosis biomarkers of various lung diseases. Application of demethylase can reverse the methylation degree changes in promoter region of Cav‐1 gene and induce the re‐expression of Cav‐1. The re‐expression of Cav‐1 makes therapeutic effect on some chronic lung diseases