Targeting pyroptosis in renal fibrosis: From molecular mechanisms to therapeutic horizons (Review)

Area of Science:

• Nephrology
• Immunology
• Cell Biology

Background:

• Pyroptosis, an inflammatory cell death, is a key driver of renal fibrosis and subsequent kidney failure.
• Dysregulated pyroptosis creates a cycle of chronic inflammation and extracellular matrix deposition in the kidneys.

Purpose of the Study:

• To review the regulatory mechanisms of renal pyroptosis, focusing on molecular triggers and execution pathways.
• To evaluate current and advanced therapeutic strategies for managing renal fibrosis by targeting pyroptosis.

Main Methods:

• Integration of preclinical in vivo and in vitro studies with clinical observations.
• Systematic evaluation of pharmacological interventions and multi-target synergistic strategies.
• Discussion of advanced therapeutic approaches like nanoparticle-based delivery systems.

Main Results:

• Pyroptosis, involving NLRP3 and GSDMD, directly contributes to the progression of renal fibrosis.
• Expression levels of NLRP3 and GSDMD in patients correlate with the severity of renal fibrosis.
• Targeting pyroptosis signaling pathways presents a viable therapeutic avenue for renal fibrosis.

Conclusions:

• Understanding pyroptosis mechanisms is crucial for developing effective treatments for renal fibrosis.
• Pharmacological interventions and advanced delivery systems show promise in managing pyroptosis-driven renal fibrosis.
• Bridging research and clinical applications is essential for advancing renal fibrosis management.