Page 65 - 22-0424

The International Journal of the Royal Society of Thailand
Volume XI - 2019

of the genes (Saez-Rodriguez et al., 2019). Moreover, kidney is a complex organ
which different cells of the nephron response to injury differently. Thus, this will
limit the utility of WGS to describe structural organization of kidney and

pathophysiology at a molecular level. In current practice, the benefit of WGS is
shown in detection of Mendelian disorders in maternal prenatal diagnosis.

The introduction of the next generation sequencing enables us to sequence
massive amount of genome. By having more sequenced genetic materials,
we could compare the genome sequences between disease population and non-
disease population. These will lead to the development of new targeted therapy
in the future. Recently, introduction of single- cell transcriptomic technique,
epigenetic assay, and proteomic assays have become the promising techniques
to explain the pathophysiology of AKI (Kiryluk et al., 2018).

Epigenetics

Epigenetics were defined as the study of changes in gene expressions that
are not originate from alterations in the genome DNA sequence (Chmielewski
et al., 2011; Reddy and Natarajan, 2015; Wanner and Bechtel-Walz, 2017). These
changes are often heritable. Three major processes including DNA methylation,
non-coding RNA and histone modifications reversibly altered the gene expressions
(Reddy and Natarajan, 2015). Methylation of DNA promoter regions (5 position
th
of cytosine) cause blockage of DNA transcription by interfere with transcriptional
factor binding and increase repressor complexes (Bird and Wolffe, 1999).
Non-coding RNA is RNA that not being translated into proteins. But it can alter
protein synthesis via epigenetic mechanisms. One example of non-coding RNA
is MicroRNA (miRNA), although it contain only 20-24 nucleotide-long, it able to
interfere various gene expressions (Ebert and Sharp, 2012). Histone modifications

are post-translational modifications to histone protein; for instance, acetylation
and methylation. Histone acetylation involves histone acetyltransferases (HATs)
by adding acetyl group to histone increasing DNA transcriptions by relaxing the
DNA string (Fontecha-Barriuso et al., 2018). Histone demethylases (HDM) remove
methyl group in arginine and lysine residues at histone tails causing either enhance
or suppress in gene transcription (D'Oto et al., 2016).

An example of epigenetic study in AKI was the study of apelin-13 in
ischemic-reperfusion injury of kidney in rat model (Chen et al., 2015; Pekowska
et al., 2010). Apelin-13 inhibited histone methylation causing markedly reduced

Phatadon Sirivongrangson
Nattachai Srisawat 59

11/7/2565 BE 13:28
_22-0424(055-076)7.indd 59
_22-0424(055-076)7.indd 59 11/7/2565 BE 13:28