Abstract: FR-PO963
Expression of Acsm2, a Kidney Specific Gene, Parallels the Structural and Functional Maturity of Proximal Tubular Cells
Session Information
- Pathology and Lab Medicine: Basic
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1601 Pathology and Lab Medicine: Basic
Authors
- Watanabe, Hirofumi, University of Virginia School of Medicine, Charlottesville, Virginia, United States
- Paxton, Robert L., University of Virginia School of Medicine, Charlottesville, Virginia, United States
- Sequeira Lopez, Maria Luisa S., University of Virginia School of Medicine, Charlottesville, Virginia, United States
- Gomez, Roberto Ariel, University of Virginia School of Medicine, Charlottesville, Virginia, United States
Background
Acyl-CoA synthetase medium-chain family member 2 (Acsm2) gene was first identified and cloned by our group as a kidney specific “KS” gene. Acms2 may participate in fatty acid metabolism and glycine conjugation pathways. However, little has been reported on Acsm2, and the expression pattern and function of it remain to be clarified.
Methods
The expression pattern of Acsm2 was investigated with RT-PCR using RNA extracted from multiple organs of adult C57BL/6 mice and kidneys at multiple age. Immunohistochemistry for Acsm2 was performed in kidney or liver tissue sections. In situ hybridization was performed using digoxigenin-labeled RNA probes for mRNA of Acsm2. We also investigated the kidneys from mice subjected to partial unilateral ureteral obstructions (pUUO) and chronic kidney disease (CKD) with total renin gene knockout or conditional knockout of integrin beta 1 gene in cells from the renin progeny using aforementioned methods. Data from the Encyclopedia of DNA Elements (ENCODE) project was analyzed to examine the epigenetic state at Acsm2 locus in each organ of mice.
Results
We found that Acsm2 was expressed in the kidney samples at high level. The expression of Acsm2 in the liver was less than 1/10,000 of the expression in the kidney. No other organs tested expressed Acsm2. Immunohistochemistry and in situ hybridization revealed that Acsm2 was highly expressed in the proximal tubular cells in normal adult mice. In contrast, Acsm2 was not detected in liver. The expression level of Acsm2 in kidneys was at a low level in newborn mice, increased with development, and reached a plateau by 2 months of age. With pUUO and CKD, the expression of Acsm2 in the proximal tubules was significantly decreased according to the severity of the renal impairment. Analysis using ENCODE database revealed that Acsm2 locus in mice has specific histone modifications that are related to the active enhancer and promoter and transcription only in kidney cells.
Conclusion
The Acsm2 gene is specifically expressed in proximal tubules, and not in other tissues. The expression of Acsm2 parallels the structural and functional maturation of proximal tubular cells. Downregulation of its expression in several models of kidney disease suggests that Acms2 may serve as a novel marker of proximal tubular injury and/or dysfunction.
Funding
- NIDDK Support