TY - JOUR
T1 - Mechanistic insights into the role of serum-glucocorticoid kinase 1 in diabetic nephropathy
T2 - A systematic review
AU - Noor, Saba
AU - Mohammad, Taj
AU - Ashraf, Gulam M.
AU - Farhat, Joviana
AU - Bilgrami, Anwar L.
AU - Eapen, Mathew Suji
AU - Sohal, Sukhwinder Singh
AU - Yadav, Dharmendra Kumar
AU - Hassan, Md Imtaiyaz
N1 - Publisher Copyright:
© 2021
PY - 2021/12/15
Y1 - 2021/12/15
N2 - 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.
AB - 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.
KW - Diabetic nephropathy
KW - Epithelial sodium channel
KW - Hyperglycemia
KW - Renal fibrosis
KW - Serum glucocorticoid kinase
KW - Therapeutic targeting
UR - http://www.scopus.com/inward/record.url?scp=85118363568&partnerID=8YFLogxK
U2 - 10.1016/j.ijbiomac.2021.10.165
DO - 10.1016/j.ijbiomac.2021.10.165
M3 - Review article
C2 - 34715204
AN - SCOPUS:85118363568
SN - 0141-8130
VL - 193
SP - 562
EP - 573
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
ER -