1.Upregulation of Megalin, Cubilin, NGAL mRNA expression in kidney may represent tubular injury and apoptosis in chronic condition of rat diabetic model
Muhammad Mansyur Romi ; Nungki Anggorowati ; Dara Syifa Maulida ; Muhammad Wishka Al Hafiidh Suskalanggeng ; Wiwit Ananda Wahyu Setyaningsih ; Dwi Cahyani Ratna ; Nur Arfian
The Medical Journal of Malaysia 2021;76(1):87-92
Introduction: Diabetes mellitus (DM) leads to microvascular
injury development and produces diabetes nephropathy
(DN) with proteinuria, tubular injury, apoptosis and
autophagy with upregulation of Bax, BASP and mTORC-1.
Megalin, Cubilin and Neutrophil Gelatinase Associated
Lipocalin (NGAL) play role in acute pathological condition of
kidney injury, however its expression in chronic and slowly
progressive kidney injury such as DN has not been
elucidated yet. This study focuses upregulation of Megalin,
Cubilin and NGAL in association with tubular injury and
apoptosis in DN condition.
Materials and methods: Diabetic condition was performed
with intraperitoneal injection of Streptozotocin 60 mg/kg
body weight (BW) in Sprague Dawley rats (2 months old,
n=24), and were kept for 1, 2, and 4 months (DM1, DM2, and
DM4, respectively). Control group was injected with NaCl
0.9%. Serum glucose level and proteinuria score were
assessed, furthermore tubular injury score was quantified
based on Periodic-Acid Schiff (PAS) staining. Reverse
Transcriptase-PCR (RT-PCR) was carried out for NGAL,
Megalin, Cubilin, m-TOR, Bax, and BASP-1 mRNA
expression. Data were analyzed using SPSS 22 software.
Results: DM led to kidney injury in this model with
significant higher glucose level, proteinuria and tubular
injury, especially in DM4 group which represented chronic
phase of DN and CKD. These findings associated with
upregulation of Megalin,Cubilin and NGAL mRNA
expression in DM groups, especially in DM4 group. DM4
group also revealed higher expression of Bax, BASP and
mTOR mRNA expression which demonstrated apoptosis.
Conclusion: Megalin, Cubilin and NGAL upregulation may
represent tubular injury and apoptosis as progression of
DN.