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Long non-coding RNA CHCHD4P4 promotes epithelial-mesenchymal transition and inhibits cell proliferation in calcium
1Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Abstract:
Kidney stone disease is a major cause of chronic renal insufficiency. The role of long non-coding RNAs (lncRNAs) in calcium oxalate-induced kidney damage is unclear. Therefore, we aimed to explore the roles of lncRNAs in glyoxylate-exposed and healthy mouse kidneys using microarray technology and bioinformatics analyses. A total 376 mouse lncRNAs were differentially expressed between the two groups. Using BLAST, 15 lncRNA homologs, including AU015836 and CHCHD4P4, were identified in mice and humans. The AU015836 expression in mice exposed to glyoxylate and the CHCHD4P4 expression in human proximal tubular epithelial (HK-2) cells exposed to calcium oxalate monohydrate were analyzed, and both lncRNAs were found to be upregulated in response to calcium oxalate. To further evaluate the effects of CHCHD4P4 on the cell behavior, we constructed stable CHCHD4P4-overexpressing and CHCHD4P4-knockdown HK-2 cells. The results showed that CHCHD4P4 inhibited cell proliferation and promoted the epithelial-mesenchymal transition in kidney damage and fibrosis caused by calcium oxalate crystallization and deposition. The silencing of CHCHD4P4 reduced the kidney damage and fibrosis and may thus be a potential molecular target for the treatment of kidney stones.
Insights
Long non-coding RNAs (lncRNAs) play a role in kidney stone disease. CHCHD4P4 was found to promote kidney damage and fibrosis, suggesting it as a potential therapeutic target for kidney stones.
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- Kidney stone disease is a significant contributor to chronic renal insufficiency.
- The involvement of long non-coding RNAs (lncRNAs) in calcium oxalate-induced kidney damage remains largely unexplored.
Purpose of the Study:
- To investigate the differential expression and functional roles of lncRNAs in kidney damage induced by calcium oxalate.
- To identify potential lncRNA biomarkers and therapeutic targets for kidney stone disease.
Main Methods:
- Microarray analysis and bioinformatics to identify differentially expressed lncRNAs in mouse kidneys exposed to glyoxylate.
- BLAST for identifying lncRNA homologs between mice and humans.
- Quantitative analysis of lncRNA expression in cell models (HK-2 cells) exposed to calcium oxalate monohydrate.
- Functional studies using CHCHD4P4-overexpressing and knockdown cell lines.
Main Results:
- 376 mouse lncRNAs were found to be differentially expressed between glyoxylate-exposed and healthy kidneys.
- AU015836 (mouse) and CHCHD4P4 (human) lncRNAs were upregulated in response to calcium oxalate exposure.
- CHCHD4P4 overexpression inhibited HK-2 cell proliferation and promoted epithelial-mesenchymal transition.
- CHCHD4P4 knockdown attenuated kidney damage and fibrosis in vitro.
Conclusions:
- CHCHD4P4 plays a critical role in promoting kidney damage and fibrosis associated with calcium oxalate crystallization.
- Silencing CHCHD4P4 demonstrates a therapeutic potential for treating kidney stone-induced renal pathology.
- CHCHD4P4 represents a promising molecular target for intervention in kidney stone disease.
