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All Journal Indonesian Journal of Biomedicine and Clinical Sciences
Nungki Anggorowati
Department of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
Biochemistry, Genetics & Molecular Biology Health Professions Immunology & microbiology Medicine & Pharmacology Neuroscience

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Endothelin-converting enzyme-1 mRNA expression correlates with downregulation of kallikrein and upregulation of endothelin a receptor after ureteral ligation in mice: ECE-1 downregulates Kallikrein expression upon UUO Nur Arfian; Dian Prasetyo Wibisono; Ghassani Rahman; Valerie Hassani Putri; Ardiles Varian; FBA Ummiyah; Eryna Ayu Nugra Desita; Nungki Anggorowati; Dwi Cahyani Ratna Sari
Indonesian Journal of Biomedicine and Clinical Sciences Vol 58 No 4 (2026): in press
Publisher : Published by Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/inajbcs.v58i4.33823

Abstract

Endothelin-converting enzyme-1(ECE-1), endothelin A receptor (ETAR) and kallikrein-kinin system (KKS) may play roles in the pathophysiology of kidney disease. ECE-1, an important protein responsible for endothelin-1 (ET-1) production, may contribute to renal fibrosis due to kidney obstruction. However, KKS has shown protective roles in kidney injury. In this study, we investigated the relationship between Kallikrein, ETAR, and ECE-1 mRNA expression in a unilateral ureteral obstruction (UUO) model in mice. Twenty male Swiss Webster mice (age 8-12 weeks, body weight 30-40 grams) were divided into 3 groups: negative control/Sham-operated group (SO, n=6), mice with UUO which were sacrificed on day 7 (D7UUO, n=7), and day 14 (D14UUO, n=7). Tubular injury score was analysed by Periodic Acid Schiff (PAS) staining, and immunohistochemistry of α-SMA was conducted to examine myofibroblast formation. ECE-1, Kallikrein, and ETAR mRNA expressions were quantified using reverse transcriptase-PCR (RT-PCR). UUO induced tubular injury and destruction of renal architecture, with higher scores in the D7UUO and D14UUO groups (p<0.001). Myofibroblast area fraction also revealed a significantly higher area fraction in D7UUO (p<0.001) and D14UUO (p<0.001) compared to SO. Furthermore, UUO promoted ECE-1 upregulation that was associated with Kallikrein downregulation. We also found a significantly upregulated expression of ETAR in the D14UUO group compared to the SO and D7UUO groups. Ureteral ligation may induce upregulation of ECE-1 and ETAR expression and downregulation of Kallikrein expression, leading to their contributions in kidney disease.
Co-Authors Ardiles Varian Dian Prasetyo Wibisono Dwi Cahyani Ratna Sari Eryna Ayu Nugra Desita FBA Ummiyah Ghassani Rahman Nur Arfian Valerie Hassani Putri