Transcription factor Kruppel-like factor 5 positively regulates the expression of AarF domain containing kinase 4

AarF domain containing kinase 4 (ADCK4) is identified as a candidate gene associated with hereditary nephrotic syndrome (NS). Kruppel-like factor 5 (KLF5) is reported to promote podocyte survival by blocking the ERK/p38 MAPK pathways. Both ADCK4 and KLF5 are involved in the occurrence and development of podocyte disease, but their interaction remains unclear. Firstly, we found that the mRNA levels of ADCK4 and KLF5 decreased in NS patients, and both levels showed an obvious linear relationship. Secondly, we cloned the ADCK4 promoter region and examined its promoter activity in Hela, A549, and HEK 293 cell lines. Deletion analysis showed that the region - 116/- 4 relative to the transcriptional start site (TSS) was the core region of ADCK4 promoter. Thirdly, mutation analysis showed that putative binding sites for KLF5 contributed to the ADCK4 promoter activity. In HEK293 cells, we found that KLF5 upregulated the mRNA and protein levels of ADCK4. Finally, our chromatin immunoprecipitation assay found that KLF5 could bind to the specific region of ADCK4 promoter. These results showed that KLF5 can positively regulate the transcriptional activity of ADCK4.