Abstract
A disintegrin and metalloproteinase 17 (ADAM17) is a ubiquitously expressed membrane-bound sheddase that cleaves a diverse variety of membrane-bound molecules, including cytokines, growth factors, and their receptors to activate or inactivate various cellular signaling pathways. Although it was reported that ADAM17 may mediate renal diseases, the role of ADAM17 in the regulation of normal kidney function has never been identified. The objective of this study is to investigate whether renal ADAM17 plays a role in maintaining normal kidney function and structure. Tamoxifen-inducible kidney-specific cre (Ksp) and ADAM17-floxed mice were cross-bred for generating Ksp/ADAM17-floxed mice. Injection of tamoxifen initiated deletion of the ADAM17 gene in renal tubule cells. We found that conditional kidney-specific knockout of ADAM1 7 gene (Ksp-ADAM17 -/-) decreased urinary creatinine and sodium excretion were decreased in Ksp-ADAM17 -/- mice, indicating that ADAM17 gene deficiency impairs kidney function. H&E staining showed glomerulus collapse and tubule dilation in Ksp-ADAM17 -/- mice. The epithelial cells fall off into the lumen in the renal tubule. Mesangial expansion and fibrosis were found in glomeruli in Ksp-ADAM17 -/- mice. Moreover, apoptosis was increased in tubule cells in both cortex and medulla areas in Ksp-ADAM17 -/- mice. In conclusion, ADAM17 is critical to the maintenance of normal renal function and structure.
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