Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Effects of KLF5 overexpression on renal collecting duct epithelial cell line (mIMCD-3)

ABSTRACT: Analysis of expression changes in renal collecting duct epithelial cells by adenoviral mediated Krüppel like transcription factor 5 (KLF5) overexpression. KLF5 is a key regulator of static and inflammatory stage in renal collecting duct epithelial cells. We thought these results provide insights into downstream genes of KLF5 in renal collecting duct epithelial cells. Total RNAs were isolated from adenovirally-mediated KLF5 over expressed cultured mIMCD-3 cells or control adenovirus infected mIMCD-3. We analyzed these two gene expression profiles after 24 hours after infection.

ORGANISM(S): Mus musculus

SUBMITTER: Katsuhito Fujiu

PROVIDER: E-GEOD-29323 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:To further examine the gene expression of isolated primary mouse proximal tubular epithelial cells (mPTECs) during ex vivo culture, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish the key regulatory transcription factor which was significantly altered. Primary culuture of mPTECs were cultured on culture dishes for 1 and 3 days. As compared to freshly isolated mPTECs, a 1801-gene consensus signature was identified that distinguished between day 1 and and day 3 samples. Within these genes, 78 transcriptal factors were dramatically altered. Expression of three genes (KLF5, KLF4, and CCND1) from this signature was quantified in the same RNA samples by RT-PCR. The proliferation of mouse proximal tubular epithelial cells in ex vivo culture depends on matrix stiffness. Combined analysis of the microarray and experimental data revealed that Krüppel-like factor 5 (Klf5) was the most upregulated transcription factor accompanied by Krüppel-like factor 4 (Klf4) downregulation when cells on stiff matrix. These changes were reversed by soft matrix via ERK inactivation. Knockdown of Klf5 or forced-expression of Klf4 inhibited stiff matrix-induced cell spreading and proliferation, suggesting that Klf5/Klf4 act as positive/negative regulators, respectively. Moreover, stiff matrix-activated ERK increased the protein level and nuclear translocation of mechanosensitive Yes-associated protein 1 (YAP1), which is reported to prevent Klf5 degradation. Finally, in vivo model of unilateral ureteral obstruction (UUO) revealed that matrix stiffness-regulated Klf5/Klf4 is related to the pathogenesis of renal fibrosis. In the dilated tubules of obstructed kidney, ERK/YAP1/Klf5/Cyclin D1 axis were upregulated and Klf4 was downregulated. Inhibition of collagen crosslinking by lysyl oxidase inhibitor alleviated UUO-induced tubular dilatation and proliferation with preserving Klf4 and suppressing the ERK/YAP1/Klf5/Cyclin D1 axis. This study unravels a novel mechanism how matrix stiffness regulates cellular proliferation and highlights the importance of matrix stiffness-modulated Klf5/Klf4 in the regulation of renal physiological functions and fibrosis progression. Gene expression in cultured mPTECs was measured at 0, 1 and 3 days after culturing on culture dishes.

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Effects of KLF5 overexpression on renal collecting duct epithelial cell line (mIMCD-3)

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