Low-intensity pulsed ultrasound (LIPUS) switched macrophage into M2 phenotype and mitigated necroptosis and increased HSP 70 in gentamicin-induced nephrotoxicity

Background and aim: Many attempts to control acute kidney injury (AKI) have failed due to a lack of under-standing of its pathophysiological key components. Macrophages are a crucial determinant of AKI, which can be categorized functionally as M1 pro-inflammatory and M2 anti-inflammatory macrophages. Low-intensity pulsed ultrasound (LIPUS) is currently being investigated as an immune modulator. The present study aimed to explore the potential effects of LIPUS on the polarization of renal macrophages, as well as the possible interplay between macrophage polarization and necroptosis in gentamicin-induced acute kidney injury.Method: All rats were randomly allocated into one of four groups: control, LIPUS-treated control, gentamicin acute kidney (GM-AKI), and LIPUS-treated GM-AKI. Renal functions, macrophage polarization, necroptosis, and heat shock protein-70 (HSP70) were analyzed using real-time reverse-transcriptase-polymerase chain reaction (rT-PCR), Western Blot, Enzyme-linked immunosorbent assay (ELISA) as well as immunohistological analysis.Results: we found that LIPUS markedly inhibited the expressions of M1 macrophage-related genes and promoted significantly the expression of M2 macrophages related genes. This was accompanied by an inhibition of nec-roptosis and a marked reduction of HSP-70, resulting in a reversal of gentamicin-induced renal alteration. Conclusion: Functional switching of macrophage responses from M1 into M2 seems to be a potential approach to ameliorate necroptosis as well as HSP-70 by low pulsed ultrasound waves in GM-AKI.

Automated summary

The present study found that low-intensity pulsed ultrasound (LIPUS) can inhibit the pro-inflammatory response of M1 macrophages and promote the anti-inflammatory response of M2 macrophages in acute kidney injury. It also reverses gentamicin-induced renal damage by inhibiting necroptosis and reducing the expression of heat shock protein-70.