Retracted: DLX5 gene regulates the Notch signaling pathway to promote glomerulosclerosis and interstitial fibrosis in uremic rats

Abstract

Uremia largely results from the accumulation of organic waste products normally cleared by the kidneys, which commonly accompanies kidney failure and chronic kidney disease. However, genetic investigations in a uremia remain largely unclear.This study aimed to determine the expression patterns of distal-less homeobox 5 (DLX5) in uremia rat model and further to study its effects on glomerulosclerosis and interstitial fibrosis. Uremic expression chip was applied to screen differentially expressed genes in uremia. Next, we used small interfering RNA-mediated RNA interference to specifically silence DLX5 in experimental uremic rats to understand the regulatory mechanism of DLX5. To understand effect of Notch1 signaling pathway in uremia, we also treated experimental uremic rats with γ-secretase inhibitor (GSI), an inhibitor of Notch1 signaling pathway. The expression of fibronectin (FN), laminin (LN), transforming growth factor-β1 (TGF-β1), Hes1, Hes5, and Jagged2 was determined. The semiquantitative assessment was applied to verify the effects of DLX5 on glomerulosclerosis. In the uremic expression chip, we found that DLX5 was upregulated in uremia samples, and considered to regulate the Notch signaling pathway. We found that small interfering RNA-mediated DLX5 inhibition or Notch1 signaling pathway inhibitory treatment relieved and delayed the kidney injury and glomerulosclerosis in uremia. Meanwhile, inhibition of DLX5 or Nothch1 signaling pathway reduced expression of FN, LN, Nothch1, TGF-β1, Hes1, Hes5, and Jagged2.

NKL homeobox gene activities in normal and malignant myeloid cells

“…CUL1 mediates proteasomal degradation of NOTCH1, and MAML2—activated by NANOG in HL-60 cells—acts as an activator of NOTCH-signalling [71,72]. Finally, DLX5 activates NOTCH signalling in malignant T-cells and uremic kidney [73,74], suggesting that this aberrantly expressed NKL homeobox gene may regulate NANOG expression via this pathway in NOMO-1 as well. However, the NOTCH-pathway plays a controversial role in AML, performing context-dependent either tumor suppressor or oncogenic functions [38].…”

Differential DNA Methylation Landscape in Skin Fibroblasts from African Americans with Systemic Sclerosis

“…The different outcomes of gene expression for DLX5 between the experiments could be the result of measuring gene expression in one cell type vs. across multiple cell types in skin biopsies, as well as underlying ancestral differences in gene expression. The inhibition of DLX5 in a uremic model of renal fibrosis causes a decreased expression of Notch receptors, ligands, and target genes [66]. Because Notch signaling is active in skin fibroblasts isolated from SSc patients and contributes to fibrosis in animal models [67,68], DLX5 may also regulate fibrosis through Notch signaling in SSc.…”