Expression and regulation of 1-acyl-sn-glycerol- 3-phosphate acyltransferases in the epidermis

Peter M Elias,Biao Lu,Kenneth R Feingold,Yan J Jiang,Barbara Brown,Mao Q Man

doi:10.1194/jlr.m500258-jlr200

Abstract

Phospholipids are a major class of lipids in epidermis, where they serve as a source of free fatty acids that are important for the maintenance of epidermal permeability barrier function. The phospholipid biosynthetic enzyme, 1-acyl-sn-glycerol-3-phosphate acyltransferase (AGPAT), catalyzes the acylation of lysophosphatidic acid to form phosphatidic acid, the major precursor of all glycerolipids. We identified an expression pattern of AGPAT isoforms that is unique to epidermis, with relatively high constitutive expression of mouse AGPAT (mAGPAT) 3, 4, and 5 but low constitutive expression of mAGPAT 1 and 2. Localization studies indicate that all five isoforms of AGPAT were expressed in all nucleated layers of epidermis. Furthermore, rat AGPAT 2 and 5 mRNAs increased in parallel with both an increase in enzyme activity and permeability barrier formation late in rat epidermal development. Moreover, after two methods of acute permeability barrier disruption, mAGPAT 1, 2, and 3 mRNA levels increased rapidly and were sustained for at least 24 h. In parallel with the increase in mRNA levels, an increase in AGPAT activity also occurred. Because upregulation of mAGPAT mRNAs after tape-stripping could be partially reversed by artificial barrier restoration by occlusion, these studies suggest that an increase in the expression of AGPATs is linked to barrier requirements.

Highlights

Phospholipids are a major class of lipids in epidermis, where they serve as a source of free fatty acids that are important for the maintenance of epidermal permeability barrier function
The expression pattern of mouse AGPAT (mAGPAT) in epidermis was unique. Both mAGPAT 1 and 2 mRNAs were low in murine epidermis, compared with the high expression levels of these isoforms in other tissues, including brain, heart, lung, liver, kidney, and spleen
These studies show that the expression profile of mAGPAT isoforms differs in epidermis compared with other murine tissues

Summary

Introduction

Phospholipids are a major class of lipids in epidermis, where they serve as a source of free fatty acids that are important for the maintenance of epidermal permeability barrier function. The principal function of the epidermis is to provide a protective barrier against transcutaneous water loss [1, 2] This permeability barrier is localized to the stratum corneum, where three key lipids, cholesterol and ceramides as well as free fatty acids, form the extracellular lamellar membrane structures that mediate permeability barrier function [3, 4]. Understanding the expression profile of these enzymes in epidermis, where there is a tissue-specific requirement for phospholipid synthesis for the barrier, could increase our understanding of how AGPAT participates in permeability barrier homeostasis and perhaps other epidermal functions. The aims of the present study are as follows: 1) to determine which AGPAT isoforms are expressed in the epidermis and their localization; 2) to determine the regulation of each isoform during fetal epidermal barrier development; and 3) to assess the regulation of isoform expression in relation to epidermal permeability barrier homeostasis

Objectives

Methods

Results

Conclusion