Long non-coding RNA expression profile in the kidneys of male, low birth weight rats exposed to maternal protein restriction at postnatal day 1 and day 10.

Yanhong Li,Xueqin Wang,Meifang Jin,Jian Pan,Jian Wang,Xiaozhong Li,Mengxia Li,Xing Feng

doi:10.1371/journal.pone.0121587

Abstract

BackgroundLong non-coding RNAs (lncRNAs), which are involved in a variety of biological functions and aberrantly expressed in many types of diseases, are required for postnatal development. In this study, we aimed to investigate the lncRNA profiles in low birth weight (LBW) rats with reduced nephron endowment induced by the restriction of maternal protein intake. LBW by reduced nephron endowment is a risk factor for hypertension and end-stage renal disease in adulthood.MethodsKidneys were obtained from LBW rats fed a low-protein diet throughout gestation and lactation as well as from normal control rats born from dams fed normal protein diets at postnatal day 1 (p1) and 10 (p10). The total number of glomeruli in the kidneys was counted at p10. LncRNA expression profiles were analyzed by sequencing and screening using the Agilent Rat lncRNA Array. Quantitative real-time PCR (qRT-PCR) analysis of these lncRNAs confirmed the identity of some genes.ResultsThe total number of glomeruli per kidney at p10 was significantly lower in LBW rats than in controls. A total of 42 lncRNAs were identified to be significantly differentially expressed, with fold-changes ≥2.0, between the two groups. According to correlation analysis between the differentially expressed lncRNAs and mRNAs involved in kidney development, we randomly selected a number of lncRNAs for comparison analysis between LBW and control kidneys at the two time-points, p1 and p10, using qRT-PCR. Three lncRNAs (TCONS_00014139, TCONS_00014138, and TCONS_00017119), which were significantly correlated with the mRNA expression of mitogen-activated protein kinase 4, were aberrantly expressed in LBW rats, compared with controls, at both p1 and p10.ConclusionsLncRNAs are aberrantly expressed in the kidneys of LBW rats, compared with controls, during nephron development, which indicates that lncRNAs might be involved in impaired nephron endowment.

Highlights

Low birth weight (LBW) induced by intrauterine growth restriction (IUGR) is considered to be a predisposing factor for hypertension and renal disease in adulthood [1,2,3]
According to correlation analysis between the differentially expressed Long non-coding RNAs (lncRNAs) and mRNAs involved in kidney development, we randomly selected a number of lncRNAs for comparison analysis between low birth weight (LBW) and control kidneys at the two time-points, p1 and p10, using Quantitative real-time PCR (qRT-PCR)
LncRNAs are aberrantly expressed in the kidneys of LBW rats, compared with controls, during nephron development, which indicates that lncRNAs might be involved in impaired nephron endowment

Summary

Introduction

Low birth weight (LBW) induced by intrauterine growth restriction (IUGR) is considered to be a predisposing factor for hypertension and renal disease in adulthood [1,2,3]. Reduced nephron endowment at the beginning of life may be subsequently cause a long-term risk of hypertension and renal disease in adult life [5,6,7,8]. Long non-coding RNAs (lncRNAs), which are involved in a variety of biological functions and aberrantly expressed in many types of diseases, are required for postnatal development. We aimed to investigate the lncRNA profiles in low birth weight (LBW) rats with reduced nephron endowment induced by the restriction of maternal protein intake. LBW by reduced nephron endowment is a risk factor for hypertension and end-stage renal disease in adulthood

Objectives

Methods

Results

Conclusion