Substance P Improves Renal Ischemia Reperfusion Injury Through Modulating Immune Response

Abstract

Substance P (SP), an injury-inducible messenger that mobilizes bone marrow stem cells and modulates the immune response, has been suggested as a novel target for therapeutic agents. We evaluated the role of SP as an immune cell modulator during the progression of renal ischemic/reperfusion injury (IRI). Unilateral IRI induced the transient expression of endogenous SP and the infiltration of CCR7 + M1 macrophages in injured kidneys. However, SP altered the intrarenal macrophage polarization from CCR7 + M1 macrophages to CD206 + M2 macrophages in injured kidneys. SP also modulated bone marrow-derived neutrophils and mesenchymal stromal cells after IRI. SP treatment for 4 weeks starting one week after unilateral IRI significantly preserved kidney size and length and normal tubular structures and alleviated necrotic tubules, inflammation, apoptosis, and tubulointerstitial fibrosis. The beneficial effects of SP were accompanied by attenuation of intrarenal recruitment of CD4, CD8, and CD20 cells and abnormal angiogenesis. The immunomodulatory effect of SP suggested that SP could be a promising therapeutic target for preventing the progression of acute kidney injury to chronic kidney disease.

Naringenin is a Potential Anabolic Treatment for Bone Loss by Modulating Osteogenesis, Osteoclastogenesis, and Macrophage Polarization

“…As reported in previous studies, CCR7 was used as marker for M1 macrophages while CD206 as a marker for M2 macrophages ( Vasconcelos et al, 2015 ; Chen et al, 2019 ; Peng et al, 2019 ; Kim et al, 2020 ; Chen et al, 2021 ). RAW 264.7 cells were digested and washed with PBS.…”

Involvement of neuronal tachykinin-like receptor at 86C in Drosophila disc repair via regulation of kynurenine metabolism

“… 38 SP expression is also induced in the tubules of injured kidneys by ischemia reperfusion and functions in tissue repair by modulating macrophages, bone marrow-derived neutrophils, and mesenchymal stromal cells. 39 However, for disc repair in Drosophila , Tk was not expressed in damaged discs ( Figure S7 C). Considering the distance between regenerating tissues and Tk- or TkR86C -expressing neurons, our findings indicate the non-autonomous regulation of tissue repair by Tk- or TkR86C -expressing neurons without direct innervation of damaged tissues.…”

Enteroendocrine cells and gut hormones as potential targets in the crossroad of the gut-kidney axis communication

“…In the IRI model of renal injury, tachykinin induced macrophage infiltration after 4 weeks. However, it was able to shift the polarization of intrarenal macrophages from CCR7+M1 macrophages to CD206+M2 macrophages in injured kidneys, preserving kidney size, normal tubular structures, alleviating tubular necrosis, inflammation, apoptosis, and tubulointerstitial fibrosis ( Kim et al, 2020 ). Interestingly, our in silico analysis indicates that in this model, the Tacr1 gene, which encodes the receptor for the hormone tachykinin, is downregulated (logFC = −1,07 [GSE39548]).…”