# Impact of Long-Term Cannabidiol (CBD) Treatment on Mouse Kidney Transcriptome
## 4 Discussion
\begin{table}
\begin{tabular}{l c c c} \hline \hline
**Biological Process** & **CBD Dose (mg/kg b.w.)** & **Gene Regulation** & **FDR \({}^{*}\)** & **Enrichment \({}^{**}\)** \\ \hline Cellular response to a corticosteroid stimulus & 20 & Up & 0.015 & 10.8 \\ \hline Process of qualitative biological regulation & 20 & Up & 0.010 & 1.8 \\ \hline Diurnal regulation of gene expression & 20 & Up & 0.011 & 12.8 \\ \hline Cellular response to peptides & 20 & Up & 0.010 & 4.7 \\ \hline Metabolism process of unsaturated fatty acids & 20 & Up & 0.010 & 5.1 \\ \hline Cellular response to potassium ions & 20 & Up & 0.015 & 95.2 \\ \hline Organic acid biosynthesis process & 20 & Down & 0.031 & 5.9 \\ \hline Monosaccharide biosynthesis process & 20 & Down & 0.031 & 4.3 \\ \hline The biosynthetic process of carboxylic acids & 20 & Down & 0.031 & 5.9 \\ \hline Organic acid metabolism process & 20 & Down & 0.036 & 3.2 \\ \hline The metabolism process of monocarboxylic acids & 20 & Down & 0.010 & 3.9 \\ \hline \hline \end{tabular}  
* [PERSON]’s exact test probability value for the distribution of genes in individual pathways, adjusted for multiple testing using the FDR approach; ** fold enrichment indicates the extent (fold change) to which the genes tested are over-represented in each biological process compared to expectations for the whole genome.  
\end{table} 
Table 2: _Cont._Member 2), also known as _rev-erb\(\beta\)_. This gene is a key regulator of circadian rhythms and a component of cellular metabolism [30]. As part of the biological clock, _Nr1d2_ plays a significant role in synchronizing internal physiological processes with the daily cycle [31]. Rev-erb\(\alpha\) is one of the main regulators of the negative feedback loop in the circadian clock. By repressing the expression of the _Bmal1_ gene, Rev-erb\(\alpha\) helps maintain the cyclical nature of activity and rest in clock genes, which is crucial for keeping biological rhythms in the proper phase [32]. The KEEG pathway associated with this gene and circadian rhythm regulation is presented in the Supplementary File S5. The obtained results also reveal negative regulation of genes linked to the glucocorticoid receptor (GR) signaling pathway. This pathway is essential for maintaining the body's homeostasis by regulating various physiological processes, such as the stress response, metabolism, and immune function [33]. Glucocorticoidoids, like cortisol or corticosterone in rodents, modulate the body's response to environmental stressors and are clinically used as anti-inflammatory agents [34]. Glucocorticoid activity in the kidney is vital, as it supports the regulation of water and electrolyte balance, which is crucial for maintaining blood pressure [35]. The analysis of the results of this study reveal that among the altered genes responsible for the negative regulation of glucocorticoids action is, e.g., _Fkbp5_ (FK506-binding protein 5). This gene acts as a negative regulator of glucocorticoid action. Its mechanism involves increasing cellular resistance to glucocorticoids, thereby reducing their effectiveness in response to stress [36]. In vitro experiments have shown that _Fkbp5_ disrupts the interaction between the glucocorticoid receptor (GR) complex and the transport protein dynein, delays the nuclear translocation of GR, and decreases the transcriptional activity of the gene for GR [37]. Thus, CBD seems to have potential in the regulation of glucocorticoid action, which may have several implications for metabolic, anti-inflammatory, immune-suppressive, and neurologic effects [38]. Summarizing, the present study demonstrates a dose-dependent effect of CBD on the transcriptional profile of mouse kidneys and presents genes and processes affected by a long-term CBD treatment in this model organ. The processes associated with the altered genes included the regulation of circadian rhythm cycling and glucocorticoid receptor function, which are strong candidates for further research on this compound and its potential benefits in the treatment of renal disorders.