Apobec-1 Complementation Factor (A1CF) Inhibits Epithelial-Mesenchymal Transition and Migration of Normal Rat Kidney Proximal Tubular Epithelial Cells.

Liyuan Huang,Jin Hao,Zhaomin Mao,Yanxia Hu,Zhongshi Lyu,Dongsheng Ni,Yuru Zhou,Zhicheng Liu,Li Zhou,Yaoshui Long,Yiman Li,Qin Zhou,Rui Peng,Honglian Wang,Jianing Liu

doi:10.3390/ijms17020197

Abstract

Apobec-1 complementation factor (A1CF) is a member of the heterogeneous nuclear ribonucleoproteins (hnRNP) family, which participates in site-specific posttranscriptional RNA editing of apolipoprotein B (apoB) transcript. The posttranscriptional editing of apoB mRNA by A1CF in the small intestine is required for lipid absorption. Apart from the intestine, A1CF mRNA is also reported to be highly expressed in the kidneys. However, it is remained unknown about the functions of A1CF in the kidneys. The aim of this paper is to explore the potential functions of A1CF in the kidneys. Our results demonstrated that in C57BL/6 mice A1CF was weakly expressed in embryonic kidneys from E15.5dpc while strongly expressed in mature kidneys after birth, and it mainly existed in the tubules of inner cortex. More importantly, we identified A1CF negatively regulated the process of epithelial-mesenchymal transition (EMT) in kidney tubular epithelial cells. Our results found ectopic expression of A1CF up-regulated the epithelial markers E-cadherin, and down-regulated the mesenchymal markers vimentin and α-smooth muscle actin (α-SMA) in NRK52e cells. In addition, knockdown of A1CF enhanced EMT contrary to the overexpression effect. Notably, the two A1CF variants led to the similar trend in the EMT process. Taken together, these data suggest that A1CF may be an antagonistic factor to the EMT process of kidney tubular epithelial cells.

Highlights

Apobec-1 complementation factor (A1CF) is an RNA binding protein, containing three RNA recognition motifs (RRMs) in its N-terminus [1]
In order to highlight the conservation of A1CF among species, MEGA6 software was explored to construct the phylogenetic neighbor-joing tree (NJ tree) of A1CF, and NCBI BLAST was used to calculate the identity values of these species listing on the right of phylogenetic tree
We described a novel role of A1CF in the field of mammalian kidneys other than its role in regulating apolipoprotein B (apoB) mRNA editing in mammalian small intestines

Summary

Introduction

Apobec-1 complementation factor (A1CF) is an RNA binding protein, containing three RNA recognition motifs (RRMs) in its N-terminus [1]. It has nanomolar affinity to the 11 nucleotide AU-rich region called “mooring” sequence of apolipoprotein B (apoB) mRNA to direct mediate C-to-U RNA editing of apoB mRNA transcript which results in the translational termination of a truncated protein, apoB48 rather than apoB100 [2,3,4] In this process, A1CF binds to both a cytidine deaminase named apobec-1 and nucleotide C6666 of apoB mRNA for site-specific C to U editing turning CAA to UAA stop codon [5,6]. Previous studies have demonstrated that, in addition to the intestine, A1CF is expressed in the kidneys and liver where neither ApoB mRNA nor apobec-1 is expressed, indicating that A1CF must have other biological functions more than apoB mRNA editing [9] In this regard, “mooring” sequences have drawn greater attention. Whether A1CF has a biological function during the occurrence and development of kidney disease has been an open question in view of the finding that A1CF is abundant in the kidneys

Objectives

Methods

Results

Discussion

Conclusion