Abstract
In acute kidney injury (AKI), the S3 segment of the proximal tubule is particularly damaged, as it is most vulnerable to ischemia. However, this region is also involved in renal tubular regeneration. To deeply understand the mechanism of the repair process after ischemic injury in AKI, we focused on glial cells missing 1 (Gcm1), which is one of the genes expressed in the S3 segment. Gcm1 is essential for the development of the placenta, and Gcm1 knockout (KO) is embryonically lethal. Thus, the function of Gcm1 in the kidney has not been analyzed yet. We analyzed the function of Gcm1 in the kidney by specifically knocking out Gcm1 in the kidney. We created an ischemia–reperfusion injury (IRI) model to observe the repair process after AKI. We found that Gcm1 expression was transiently increased during the recovery phase of IRI. In Gcm1 conditional KO mice, during the recovery phase of IRI, tubular cell proliferation reduced and transforming growth factor-β1 expression was downregulated resulting in a reduction in fibrosis. In vitro, Gcm1 overexpression promoted cell proliferation and upregulated TGF-β1 expression. These findings indicate that Gcm1 is involved in the mechanisms of fibrosis and cell proliferation after ischemic injury of the kidney.
Highlights
The kidney is an important organ that removes toxic waste products and excess water from the body in the form of urine, and it is essential for the maintenance of life
acute kidney injury (AKI) was replicated in an ischemia–reperfusion injury (IRI) model, and the blood urea nitrogen (BUN) level was measured as an indicator of renal function
The BUN level was significantly higher in day 1 IRI mice than in day 0 mice, and the level decreased after day 1 (Fig. 1a)
Summary
The kidney is an important organ that removes toxic waste products and excess water from the body in the form of urine, and it is essential for the maintenance of life. The progression of AKI has been shown to increase the risk of developing chronic kidney disease (CKD)[4,5] and cause deterioration of existing CKD4,6 and progression to end-stage renal disease[4,7,8]. Analysis of the genes expressed in the S3 segment is very important to understand the mechanisms of the repair process after ischemic injury and to identify a treatment approach for preventing the progression of AKI to CKD. The glial cells missing 1 (Gcm1) gene is one of the genes expressed in the S3 segment[29], and its function in the kidney is still not entirely known. The findings of this study might help better understand fibrosis and cell proliferation after ischemic kidney injury
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