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.
Highlights
The formation of kidney stones is a common urological disorder, and the number of patients presenting with this disorder is increasing
Generation of the kidney stone disease mouse model While calcium crystal deposition was undetectable in the control group (Figure 1A), several refractive irregular crystals were observed in the junction of the renal cortex and medulla in the experimental group after 5 days of glyoxylate administration (Figure 1B)
Renal stone disease is largely secondary to intra- or extra-renal urinary outflow obstruction, but crystal nephropathies can lead to significant kidney damage and renal failure [2,11]
Summary
The formation of kidney stones is a common urological disorder, and the number of patients presenting with this disorder is increasing. Calcium oxalate (CaOx) is a major constituent, accounting for more than 80% of kidney stones [1]. Acute oxalosis (such as in glyoxylate poisoning) can induce acute kidney damage due to the renal tubular blockage caused by the deposition of the CaOx crystals [2]. We found that the epithelial-mesenchymal transition (EMT) occurred in a mouse model injected with glyoxylate [5]. Several other studies have suggested that kidney fibrosis was caused by the transition of renal epithelial cells to mesenchymal cells, which is a phenomenon related to cell proliferation. Cultured mouse renal tubular epithelial cells that were stimulated by transforming growth factor-b1
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