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Gene & Protein in Disease                      DNA methylation and gene expression on rats with protein malnutrition




            Table 12. Differential DMR screening.
             Content            LPF versus CON               LPE versus CON               LPF versus LPE
                        Hyper‑methylated  Hypo‑methylated  Hyper‑methylated  Hypo‑methylated  Hyper‑methylated  Hypo‑methylated
            Whole genome    29,033        119,116        32,947         19,238        25,365         28,045
            Total promoters  3158          2096           3283          2042           2785          2920
            Proximal         1568          1028           1682           985           1340          1491
            Intermediate     998            661           1033           638           880           919
            Distant          592            407           568            419           565           510
            Total exons      5170          2879           5958          2869           4111          4728
            First exon       1423           882           1542           846           1179          1338
            Internal exon    2276          1358           2699          1347           1854          2191
            Last exon        1471           639           1717           676           1078          1199
            Total intron     3098          1853           3649          1793           2540          2903
            First intron     643            443           748            434           557           619
            Internal intron  1757          1065           2093          1040           1492          1685
            Last intron      698            345           808            319           491           599
            Total intergenic  17,607       12,288        20,057         12,534        15,929         17,494
            LPE: Early-life low-protein group, LPF: Fetal low-protein group, CON: Control group
                                                                                                           [46]
            and physiological activities through the change of gene   the abnormal expression of PI3Kp110α in hippocampus .
            expression .                                       Da Costa  et  al. gave one group of pups a 0% protein
                    [39]
              The impact of early-life malnutrition on growth   diet and the other a standard diet during lactation. The
            and development later in life has attracted a great   expression of CYP gene was significantly upregulated in
                                                                                       [47]
            deal of attention, and research has been devoted to   both 60- and 90-day-old rats . Nutritional status may
            investigating the genetic factors that contribute to the   affect the metabolism of drugs and other substances
            development of chronic diseases . In this study, we   through the regulation of the expression of CYP enzyme,
                                        [40]
            found that differential expression of genome-wide DNA   leading to disrupted hormone homeostasis and various
            methylation was mainly concentrated on mitochondrial   chronic diseases. These studies shed light on a number
            genes , including  Mt-cyb,  Mt-co1,  Mt-co3,  Mt-co2,   of ways that malnutrition caused by protein restriction
                [41]
            and Mt-nd1 , in response to environmental stimuli at   early in life can lead to genetic changes in fetuses that
                      [42]
            different stages of early-life malnutrition. Mitochondrial   have important effects on later growth and development.
            DNA has an extra-nuclear genetic function and its   However, these gene changes were not detected in this
                                                                                                    [48]
            methylation, although limited in proportion, plays   study, which may be related to protein content , feeding
            a crucial role in the development of disease . Tang   time, rat species, and test samples. Some genes exist only
                                                   [43]
            reported that the expression of Notch1 gene in pulmonary   in certain tissue structures but not in blood.
            vascular endothelial cells of 3 and 9 weeks IUGR mice was   By comparing and analyzing the significantly
            significantly decreased compared with the control group,   differentially expressed genes between LPE versus CON
            and the expression of the downstream gene Hes-1 was also   and LPF versus CON, this study found that the two groups
            significantly decreased . Kuang pointed out that a low-  shared a number of upregulated genes , such as Gimap-9,
                              [44]
                                                                                             [49]
            protein diet during pregnancy in rats may lead to IUGR in   AABR07010705.1,  AABR07031521.1, AABR07032888.1,
            offspring and significant renal impairment in adulthood.   Serinc-4, Dnah-2, Sf3b-5, and Sat-2. Comparing LPF versus
            The results showed that the abnormal expression of Wt1   CON with LPF versus LPE, Mgat2 and Car3 were common
            and Igf2 may be involved in the reduction of glomerulus   genes in the two groups. Comparing LPE versus CON with
            in IUGR rats and the occurrence of adult proteinuria,   LPF versus CON, the common downregulated gene of the
            and normal protein feeding in adulthood cannot correct   two  groups  was  Ppp1r3d.  Comparing  LPF  versus  CON
            the abnormal methylation state of Wt1 gene nor prevent   with LPF versus LPE, we found that the two groups shared
            kidney damage . Chen  et al. reported that early-life   Ddx28 and Slc12a9 genes. These gene expression changes
                         [45]
            malnutrition affects the cognitive function of young mice   may play a significant role in the growth and development
            in the senile stage, and the mechanism may be related to   of early malnourished rats . For example, Mgat2 is mainly
                                                                                   [50]

            Volume 1 Issue 2 (2022)                         17                     https://doi.org/10.36922/gpd.v1i2.169
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