TGF-beta signaling in renal disease

Area of Science:

• Nephrology
• Molecular Biology
• Cell Biology

Background:

• Transforming growth factor-beta (TGF-beta) is a key mediator in chronic kidney disease (CKD) pathobiology.
• Research has primarily focused on TGF-beta's role in fibrogenesis.
• Emerging evidence suggests TGF-beta also drives glomerular and tubular epithelial cell apoptosis and transdifferentiation in CKD.

Purpose of the Study:

• To review evidence supporting nonlinear models of TGF-beta signaling in the kidney.
• To explore the functional roles of TGF-beta in mediating apoptosis and epithelial-to-mesenchymal transdifferentiation (EMT) in progressive renal disease.
• To provide a conceptual framework for understanding TGF-beta's diverse roles in glomerular and tubulointerstitial disease.

Main Methods:

• Literature review of studies on TGF-beta signaling in chronic kidney diseases.
• Analysis of evidence for nonlinear models of TGF-beta action.
• Synthesis of findings on TGF-beta's role in apoptosis and EMT.

Main Results:

• TGF-beta signaling exhibits nonlinear models in mediating renal pathobiology.
• TGF-beta plays a significant role in both apoptosis and epithelial-to-mesenchymal transdifferentiation (EMT) in progressive kidney disease.
• Cell context-dependent models are crucial for understanding TGF-beta's multifaceted functions.

Conclusions:

• TGF-beta signaling is a central player in multiple pathomechanisms of chronic kidney disease progression.
• Understanding cell context-dependent TGF-beta signaling is essential for consolidating distinct disease progression models.
• This review offers a framework to integrate fibrogenesis, apoptosis, and EMT in CKD pathogenesis.