KIM-1 protects the kidney after injury

Acute kidney injury (AKI) arises from multiple forms of renal damage, including ischemia, toxin exposure, and urinary tract obstruction. AKI-associated inflammation exacerbates damage and can lead to development of chronic kidney disease (CKD). Kidney injury molecule-1 (KIM-1) is a mucin and immunoglobulin domain-containing transmembrane protein that is highly upregulated in the proximal tubule after kidney injury. While chronic KIM-1 expression promotes renal fibrosis and kidney failure, Li Yang, Craig Brooks, and colleagues at Harvard Medical School reveal that KIM-1 dampens early inflammatory responses and protects the kidney following injury. Mice expressing a mutant form of KIM-1 that lacks the mucin domain (KIM-1^Δmucin) were more susceptible to both ischemia-induced and toxin-induced AKI compared to control animals. Loss of the mucin domain disrupted KIM-1-mediated phagocytosis in proximal tubular cells. This reduction in phagocytosis in KIM-1^Δmucin mice reduced clearance of apoptotic and necrotic cells and luminal debris after injury, leading to increased immune infiltration and inflammation.  Moreover, KIM-1-mediated phagocytosis in proximal tubular cells from WT mice triggered PI3K-dependent downregulation of NFkB activity, resulting in an anti-inflammatory phenotype that was characterized by decreased expression of TLR4 and pro-inflammatory cytokines, and reduced macrophage activation. Taken together, these data establish a protective role for KIM-1 in response to AKI. The accompanying image shows post ischemic kidney tissue from WT mice that was stained for KIM-1 (red), active caspase 3 to label apoptotic cells (green), and DAPI (blue). Differential interference contrast (DIC) microscopy was used to visualize kidney structure and the DIC image was overlaid with the fluorescent images. KIM-1-expressing proximal tubule cells bind caspase 3 positive apoptotic cells. 

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