Open Access

ARTICLE

Exploring the Role of SGK1 in Kidney Physiology: Insights from Transcriptomic Analysis

Chieh-Jen Wu^1,#, Yu-He Li^2,#, Hsin-Hung Chen^3,*

1 Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, 813414, Taiwan
2 Department of Laboratory Medicine, Zuoying Armed Forces General Hospital, Kaohsiung, 813204, Taiwan
3 Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, 813414, Taiwan

* Corresponding Author: Hsin-Hung Chen. Email:
# Chieh-Jen Wu and Yu-He Li contributed equally to this work

(This article belongs to the Special Issue: Heart-Kidney Interactions: Mechanisms in Metabolic Dysfunction and Organ Injury)

BIOCELL 2025, 49(5), 857-872. https://doi.org/10.32604/biocell.2025.064071

Received 04 February 2025; Accepted 18 April 2025; Issue published 27 May 2025

Abstract

Background: Serum- and glucocorticoid-induced kinase 1 (SGK1) is a member of the serine/threonine kinase family, playing a crucial role in regulating ion channel function, hormone secretion, cellular growth, survival mechanisms, and neuronal activity. SGK1 is implicated in kidney diseases, hypertension, and metabolic syndromes, influencing salt intake, renal growth, and renal potassium (K⁺) excretion during mineralocorticoid overdose. Although SGK1’s renal functions have been explored, comprehensive identification of SGK1-related genes and signaling cascades remains limited. Objectives: This research sought to explore the cellular mechanisms and signaling pathways influenced by SGK1 in rat kidney cells. Methods: NRK-52E cells, derived from rat kidneys, were exposed to the SGK1 inhibitor GSK 650394 (GSK) at doses of 50, 100, and 200 μM. A comparative transcriptomic approach was employed, utilizing mRNA sequencing (RNA-seq) and differential gene expression (DEG) analysis. To investigate key signaling pathways and molecular mechanisms, analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were carried out. Results: In total, 13,987 genes were detected, with differential expression observed across treatment groups. Specifically, 749 DEGs (401 upregulated, 348 downregulated) were identified in the 50 μM group, 2267 DEGs (897 upregulated, 1370 downregulated) in the 100 μM group, and 5631 DEGs (2547 upregulated, 3084 downregulated) in the 200 μM group. A total of 176 DEGs were consistently present across all treatment groups (adjusted p-value < 0.05; |log₂ fold change| > 1). Enrichment analysis revealed that these genes play a significant role in pathways potentially associated with SGK1 regulation. Conclusion: Through RNA-seq and DEG analysis, potential target genes and signaling pathways influenced by SGK1 in rat kidney cells were identified, providing a basis for future investigations into SGK1-associated molecular mechanisms and physiological roles in the kidney.

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