Mechanistic insights into the role of serum-glucocorticoid kinase 1 in diabetic nephropathy: A systematic review

Saba Noor, Taj Mohammad, Gulam M. Ashraf, Joviana Farhat, Anwar L. Bilgrami, Mathew Suji Eapen, Sukhwinder Singh Sohal, Dharmendra Kumar Yadav, Md Imtaiyaz Hassan

    Research output: Contribution to journalReview articlepeer-review

    7 Scopus citations

    Abstract

    Aberrant expression of serum-glucocorticoid kinase 1 (SGK1) contributes to the pathogenesis of multiple disorders, including diabetes, hypertension, obesity, fibrosis, and metabolic syndrome. SGK1 variant is expressed in the presence of insulin and several growth factors, eventually modulating various ion channels, carrier proteins, and transcription factors. SGK1 also regulates the enzymatic activity of Na+ K+ ATPase, glycogen synthase kinase-3, ubiquitin ligase Nedd4-2, and phosphomannose mutase impacting cell cycle regulation, neuroexcitation, and apoptosis. Ample evidence supports the crucial role of aberrant SGK1 expression in hyperglycemia-mediated secondary organ damage. Diabetic nephropathy (DN), a dreadful microvascular complication of diabetes, is the leading cause of end-stage renal failures with high morbidity and mortality rate. The complex pathogenesis of DN encompasses several influencing factors, including transcriptional factors, inflammatory markers, cytokines, epigenetic modulators, and abnormal enzymatic activities. SGK1 plays a pivotal role by controlling various physiological functions associated with the occurrence and progression of DN; therefore, targeting SGK1 may favorably influence the clinical outcome in patients with DN. This review aimed to provide mechanistic insights into SGK1 regulated DN pathogenesis and summarize the evidence supporting the therapeutic potential of SGK1 inhibition and its consequences on human health.

    Original languageBritish English
    Pages (from-to)562-573
    Number of pages12
    JournalInternational Journal of Biological Macromolecules
    Volume193
    DOIs
    StatePublished - 15 Dec 2021

    Keywords

    • Diabetic nephropathy
    • Epithelial sodium channel
    • Hyperglycemia
    • Renal fibrosis
    • Serum glucocorticoid kinase
    • Therapeutic targeting

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