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

PLOS ONE, Dec 2019

Background 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. 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. Methods Kidneys 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. Results The 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. Conclusions 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.

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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

March 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 0 1 2 Xueqin Wang 0 1 2 Mengxia Li 0 1 2 Jian Pan 0 1 2 Meifang Jin 0 1 2 Jian Wang 0 1 2 Xiaozhong Li 0 1 2 Xing Feng 0 1 2 0 1 Department of Nephrology, Children's Hospital of Soochow University , Suzhou , China , 2 Institute of Pediatric Research, Children's Hospital of Soochow University , Suzhou , China , 3 Department of Neonatology, Children's Hospital of Soochow University , Suzhou , China 1 Data Availability Statement: Raw and processed microarray data have been deposited in the National Center for Biotechnology Information Gene Expression Omnibus (series accession number , GSE64239) 2 Academic Editor: Garyfalia Drossopoulou, National Centre for Scientific Research Demokritos , GREECE - Funding: This work was supported by grants from the National Natural Science Foundation of China (81370773), the Natural Science Foundation of Jiangsu Province (BK2012604), and the Natural Science Foundation for Research Projects in the Colleges and Universities of Jiangsu Province 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. 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. Kidneys 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. The 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 (12KJB320006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. 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. 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. Low birth weight (LBW) induced by intrauterine growth restriction (IUGR) is considered to be a predisposing factor for hypertension and renal disease in adulthood [13]. IUGR often leads to reduced nephron endowment in LBW infants. A linear relationship between nephron number and birth weight was previously identified in children and adults [4]. Reduced nephron endowment at the beginning of life may be subsequently cause a long-term risk of hypertension and renal disease in adult life [58]. However, the underlying mechanism of how LBW is linked to reduced nephron endowment remains to be established. Long non-coding RNAs (lncRNAs) are defined as non-coding RNAs that are longer than 200 nucleotides in length [9]. Accumulated evidence has indicated that lncRNAs exhibit important roles in various biological processes [9, 10]. The aberrant regulation of lncRNAs has been shown to be associated with a variety of human diseases, such as neurological disorders, heart diseases, and kidney disorders [1114]. To date, a few studies on the roles of lncRNAs, as crucial regulators, during normal development have been reported [1519]. Sauvageau et al. revealed that lncRNAs are required for brain development by using multiple knockout mouse models [17]. Zhu et al. suggested that lncRNAs might be involved in heart development [18]. In renal development, a previous study suggested that mesodermal specific cDNA or transcripts and H19, an imprinted gene, are developmentally regulated, and their concomitant decreased expression might be responsible for the perturbed epithelial and mesenchymal interactions leading to dysmorphogenesis of the metanephros [20]. However, little is known about the overall expression status (...truncated)


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Yanhong Li, Xueqin Wang, Mengxia Li, Jian Pan, Meifang Jin, Jian Wang, Xiaozhong Li, Xing Feng. 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, PLOS ONE, 2015, Volume 10, Issue 3, DOI: 10.1371/journal.pone.0121587