Notch signaling in diabetic kidney disease: recent progress

Area of Science:

• Nephrology
• Endocrinology
• Molecular Biology

Background:

• Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM) and a leading cause of end-stage renal disease (ESRD).
• The global incidence of DKD is rising, necessitating novel treatment strategies and improved prognosis.
• The Notch signaling pathway plays a critical role in DKD pathogenesis.

Purpose of the Study:

• To elucidate the multifaceted roles of the Notch signaling pathway in DKD.
• To explore the interactions between Notch signaling and other pathways implicated in DKD progression.
• To identify potential therapeutic targets within the Notch pathway for DKD treatment.

Main Methods:

• Review and synthesis of existing literature on Notch signaling in DKD.
• Analysis of molecular mechanisms underlying Notch pathway involvement in kidney damage.
• Examination of interactions with TGF-β, Wnt/β-catenin, mTOR, AMPK, and autophagy pathways.

Main Results:

• Notch signaling contributes to glomerular endothelial dysfunction and filtration barrier damage.
• It influences podocyte epithelial-mesenchymal transition (EMT) and dedifferentiation.
• Notch signaling is implicated in tubulointerstitial fibrosis and proximal tubule cell dedifferentiation, as well as macrophage polarization.

Conclusions:

• The Notch signaling pathway is a key player in DKD pathogenesis through diverse cellular and molecular mechanisms.
• Interactions with other signaling cascades highlight the complexity of DKD.
• Targeting the Notch pathway presents a promising avenue for developing novel DKD therapeutics.