Arginine Alters miRNA Expression Involved in Development and Proliferation of Rat Mammary Tissue.

Gang Zhou,Jun Zhang,Mengzhi Wang,Juan J Loor,Liangyu Hu,Lianmin Chen,Jingwen Zhao,Qiaoyun Xu,Feifan Wu

doi:10.3390/ani11020535

Abstract

Simple SummaryMiRNAs are small noncoding RNAs that regulate a variety of developmental and physiological processes, with many having well-defined developmental and cell-type specific expression patterns. Aspects of the cell cycle such as cell differentiation, proliferation and apoptosis can be regulated by miRNA, underscoring an unexplored link between arginine supply and mammary tissue function during lactation. The specific objective of the present study was to determine miRNA profiles in mammary tissue at the end of lactation in response to enhanced dietary supply of arginine. Our results indicate that arginine may potentially be involved in the development of rat mammary glands through miRNA.This study was designed to determine the effects of dietary arginine on development and proliferation in rat mammary tissue through changes in miRNA profiles. Twelve pregnant Wistar rats were allocated randomly to two groups. A basal diet containing arginine or the control diet containing glutamate on an equal nitrogen basis as the arginine supplemented diet were used. The experiment included a pre-experimental period of four days before parturition and an experimental period of 17 days after parturition. Mammary tissue was collected for histology, RNA extraction and high-throughput sequencing analysis. The greater mammary acinar area indicated that arginine supplementation enhanced mammary tissue development (p < 0.01). MicroRNA profiling indicated that seven miRNA (miR-206-3p, miR-133a-5p, miR-133b-3p, miR-1-3p, miR-133a-3p, miR-1b and miR-486) were differentially expressed in response to Arginine when compared with the glutamate-based control group. In silico gene ontology enrichment and KEGG pathway analysis revealed between 240 and 535 putative target genes among the miRNA. Further verification by qPCR revealed concordance with the differential expression from the sequencing results: 17 of 28 target genes were differentially expressed (15 were highly expressed in arginine and 2 in control) and 11 target genes did not have significant difference in expression. In conclusion, our study suggests that arginine may potentially regulate the development of rat mammary glands through regulating miRNAs.

Highlights

It is well known that the mammary gland is a central organ for milk synthesis, development and metabolism of the mammary gland will affect the production of milk components such as fat and protein
Further metaanalysis by Lapierre proved that the average uptake: output ratio averages 2.45 no matter the protein sources or levels [25], which might indicate that the arginine that had been taken basically does not participate in the formation of structural protein of the mammary gland
Based on the upregulation of target genes, we propose that the physiological phenomenon of hematopoiesis and angiogenesis is a significant part of mammary tissue activated by metabolism of arginine

Summary

Introduction

It is well known that the mammary gland is a central organ for milk synthesis, development and metabolism of the mammary gland will affect the production of milk components such as fat and protein. The proliferation and differentiation of mammary are affected by many factors, such as hormones, vitamins, amino acids and trace elements [5]. These factors affect the proliferation and differentiation of mammary epithelial cells. Arginine, as an essential amino acid for newborns and conditionally-essential for adult mammals, is considered a “functional” amino acid in the body. It does promote the proliferation and differentiation of mammary cells, and promotes protein biosynthesis [6]

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