Imbalance between Endothelin-1 and eNOS expression associates with tubular injury in mice with 5/6 subtotal nephrectomy

Introduction: Chronic Kidney Diseases (CKD) leads to kidney fibrosis which characterized by tubular injury and atrophy with interstitial fibrosis. Endothelin-1 (ET-1) and endothelial Nitrite Oxide Synthase (eNOS) are known to play role in CKD and kidney fibrosis, although their correlation with tubulo-interstitial injury have not been understood clearly. Methods: 5/6 Subtotal Nephrectomy (SN) was performed in male Swiss Background mice to induce CKD. Sham operation (SO, n=5) procedure was performed on mice as control. The mice were sacrificed in day 7 (1N, n=5) and day 28 (4N, n=5) after operation. We measured creatinine serum to assess renal function. Tubular injury score was quantified based on Periodic-Acid Schiff (PAS) staining. Prepro-ET-1 and eNOS were quantified using RT-PCR. Results: SN1N and SN4N groups had significant higher of serum creatinine and tubular injury from SO group. Densitometry analysis of RT-PCR revealed up-regulation of prepro-ET-1 mRNA expression in SN1N and SN4N (p<0.05 vs SO). Meanwhile, we found a significant increase of eNOS expression in SN1N, and then it reduced significantly in SN4N. We found significant parallel correlation between ET-1 and tubular injury expression (r: 0.768;p<0,05), meanwhile there were insignificant inverse correlation between eNOS and tubular injury (r: -0.354;p>0.05). Conclusion: eNOS might play role as a counterbalance in the up regulation of ET-1 in acute condition after SN. However, it failed in chronic condition. These lead to deterioration of renal function and tubular injury. An imbalance between ET-1 and eNOS expression in chronic CKD model might play role in profound renal damage. © 2020 Elsevier B.V., All rights reserved.