Substance P Improves Renal Ischemia Reperfusion Injury Through Modulating Immune Response

Area of Science:

• Nephrology
• Immunology
• Regenerative Medicine

Background:

• Substance P (SP) is an injury-inducible peptide involved in immune response and stem cell mobilization.
• Renal ischemic/reperfusion injury (IRI) triggers inflammatory responses and immune cell infiltration in the kidneys.
• SP's role in modulating immune cells during renal IRI progression requires further elucidation.

Purpose of the Study:

• To investigate the immunomodulatory role of endogenous and exogenous Substance P (SP) in renal ischemic/reperfusion injury (IRI).
• To assess the therapeutic potential of SP in mitigating kidney damage and fibrosis following IRI.

Main Methods:

• Induction of unilateral renal IRI in a preclinical model.
• Evaluation of endogenous SP expression and immune cell infiltration (macrophages, neutrophils, lymphocytes) post-IRI.
• Administration of SP treatment starting one week after IRI and assessment of kidney morphology, inflammation, apoptosis, and fibrosis after 4 weeks.
• Analysis of angiogenesis and specific immune cell populations (CD4, CD8, CD20).

Main Results:

• Unilateral IRI induced transient endogenous SP expression and M1 macrophage infiltration.
• SP treatment shifted intrarenal macrophage polarization from M1 to M2 phenotype.
• SP administration preserved kidney size, tubular structures, and reduced necrosis, inflammation, apoptosis, and fibrosis.
• SP treatment attenuated the recruitment of CD4, CD8, and CD20 cells and abnormal angiogenesis.

Conclusions:

• Substance P acts as a key immunomodulator during renal IRI.
• SP treatment demonstrates significant renoprotective effects by modulating macrophage polarization and reducing inflammation and fibrosis.
• SP represents a promising therapeutic target for preventing the progression of acute kidney injury to chronic kidney disease.