Differential Expression Profiles of Orphan Nuclear Receptors (NR4A) and N-myc Downstream-Regulated Gene Family (NDRG) in Patients with Inflammatory Bowel Disease
Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Publisher
MDPI AG
Date Issued
2026
Author(s)
Fonseca-Camarillo, Gabriela
Aguilar-León, Diana
Barreto-Zuñiga, Rafael
Martínez-Benítez, Braulio
Yamamoto-Furusho, Jesús K.
Type
text::journal::journal article
Abstract
NDRG1 protein engages with the orphan nuclear receptor NR4A1, effectively suppressing the transcriptional activity of NF-κB and influencing the inflammatory response. However, the specific roles of the NDRG family and NR4A transcription factors in inflammatory bowel disease (IBD) remain poorly defined, particularly regarding potential differential mechanisms between ulcerative colitis (UC) and Crohn’s disease (CD). We hypothesize that NDRG–NR4A interactions are differentially regulated in UC versus CD, contributing to disease-specific modulation of NF-κB signaling and inflammatory responses. Therefore, the aim was to analyze gene and protein expression of both protein families (NDRGs: NDRG1, NDRG2, NDRG3, and NDRG4; and NR4A: NR4A1, NR4A2, and NR4A3), their contributions to UC and CD, and their association with disease severity. In this cross-sectional and comparative study, we assess gene and protein expression of NR4A and NDRG1-4 in 38 UC patients, 10 CD patients, and 18 controls. Gene and protein expression levels were measured by RT-PCR (mucosa) and immunohistochemistry (colonic tissue), respectively. The colonic mucosa from remission UC patients showed upregulation of NDRG2 and the nuclear receptor genes NR4A1-3 compared with controls. NDRG4 was upregulated in active UC patients compared with controls. NDRG1 was downmodulated in active and remission UC patients compared with controls. All differences were statistically significant (p < 0.05). Decreased NR4A2 gene expression was associated with high-sensitivity C-reactive protein (p = 0.030) and erythrocyte sedimentation rate levels (p = 0.001). Our results provide the first evidence of differential alterations in the NDRG–NR4A axis in UC and CD, which could modulate NF κB signaling and the inflammatory profile differently in each disease, opening the possibility of new therapeutic options. © The authors © MDPI © International Journal of Molecular Sciences.
License
Acceso Abierto
How to cite
Fonseca-Camarillo, G., Furuzawa-Carballeda, J., Aguilar-León, D., Barreto-Zuñiga, R., Martínez-Benítez, B., & Yamamoto-Furusho, J. K. (2026). Differential Expression Profiles of Orphan Nuclear Receptors (NR4A) and N-myc Downstream-Regulated Gene Family (NDRG) in Patients with Inflammatory Bowel Disease. International Journal of Molecular Sciences, 27(11), 4769. https://doi.org/10.3390/ijms27114769