Abstract: FR-PO052
The LncRNA Profile in Control and Ischemically Injured Kidneys of Old Mice
Session Information
- AKI: Tubules, Metabolism, New Models
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Kaucsár, Tamás, Semmelweis University, Budapest, Hungary
- Hamar, Peter, Semmelweis University, Budapest, Hungary
Background
The expression profile of lncRNA is hardly known in the control and injured kidneys of old mice. We investigated the influence of aging on the lncRNA profile after renal ischemia-reperfusion (IR) injury in mice.
Methods
The left renal pedicle of adult (9.4±0.3 months, n=7) and old (28.5±1.2 months, n=8) C57BL/6N mice was clamped for 20 min. The right kidney was left intact. Plasma urea and urine NGAL (uNGAL) were measured prior to and 7 days after reperfusion. On day 7 tubular injury was evaluated by histology (PAS, HE) and KIM1 mRNA (qPCR) expression. The extent of fibrosis (FN1) and senescence (p21) was analyzed with qPCR. Long non-coding RNA profile (90 lnc) was examined with qPCR array.
Results
Older mice had higher baseline uNGAL (old: 285.7±93.8 ng/mg Crea vs. adult: 78.0±9.1 ng/mg Crea, p<0.05) and milder kidney injury (p<0.05). KIM1 (8.3x; p<0.001), FN1 (2x; p=0.05) and p21 (3.8x; p<0.05) mRNA levels were higher in their non-ischemic kidneys relative to the adult group. There was no significant difference in baseline plasma urea levels between the two groups (old: 75.9±10.2 mg/dl vs. adult: 57.6±5.3 mg/dl). Following IR tubular injury increased in both groups (p<0.05) with KIM1 (adult: 202x, old: 19.5x, p<0.0001) and FN1 (adult: 8.5x, old: 3x, p< 0.001) mRNA compared to the contralateral control kidneys. uNGAL level was higher after IR compared to the baseline (old: 3817±1975 ng/mg Crea , p<0.0001; adult: 2833±1201 ng/mg Crea, p<0.001). p21 mRNA increased only in the ischemic kidneys (4.5x, p<0.01), compared to the contralateral control. The plasma urea concentration increased only in the old group following 7 days of reperfusion (140.7±25.6 mg/dl, p<0.01). From the 81 measureable lncRNAs 8 increased and 1 decreased only by IR. Old age only influenced 1 lncRNA expression. Further 12 lncRNA expression was influenced by both IR and old age.
Conclusion
Our results demonstrated significant tubular damage and decreased renal function in the kidneys of old mice, in accordance with the literature. We have also found that several lncRNAs were differentially expressed in old and adult mice in both the control and ischemic kidneys.
New National Excellence Program (Human Resources Department)
Funding
- Government Support - Non-U.S.