Treatments for Inflammation Publications

Dipeptidase-1 governs renal inflammation during ischemia reperfusion injury

Importantly, the study also confirmed the mechanism of action of two DPEP-1 inhibitors, the LSALT peptide (Metablok) and cilastatin that effectively protected the kidney during ischemia reperfusion injury. Both the LSALT peptide and cilastatin are protected by composition and method of use patents for AKI respectively and held by Arch Biopartners.

Publication Details

Arthur Lau, Jennifer J. Rahn, Mona Chappellaz, Hyunjae Chung, Hallgrimur Benediktsson, Dominique Bihan, Anne Von Mässenhausen, Andreas Linkermann, Craig N. Jenne, Stephen M. Robbins, Donna L. Senger, Ian A. Lewis, Justin Chun and Daniel A. Muruve


The mechanisms that drive leukocyte recruitment to the kidney are incompletely understood. Dipeptidase-1 (DPEP1) is a major neutrophil adhesion receptor highly expressed on proximal tubular cells and peritubular capillaries of the kidney. Renal ischemia reperfusion injury (IRI) induces robust neutrophil and monocyte recruitment and causes acute kidney injury (AKI). Renal inflammation and the AKI phenotype were attenuated in Dpep1−/− mice or mice pretreated with DPEP1 antagonists, including the LSALT peptide, a nonenzymatic DPEP1 inhibitor. DPEP1 deficiency or inhibition primarily blocked neutrophil adhesion to peritubular capillaries and reduced inflammatory monocyte recruitment to the kidney after IRI. CD44 but not ICAM-1 blockade also decreased neutrophil recruitment to the kidney during IRI and was additive to DPEP1 effects. DPEP1, CD44, and ICAM-1 all contributed to the recruitment of monocyte/macrophages to the kidney following IRI. These results identify DPEP1 as a major leukocyte adhesion receptor in the kidney and potential therapeutic target for AKI.


Science Advances - February 2022, Cover Image
“Given the abundant expression of DPEP1 in the kidney, we postulated that DPEP1 could also play a role in renal inflammation in the context of nonmicrobial and non–drug-induced kidney injury. In this study, we show that DPEP1 regulates the adhesion of neutrophils and monocytes to the peritubular capillaries during renal IRI and contributes to the severity of AKI.”

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