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

Xi Chen1, Shuang Liu1, Jiahe Chen1

  • 1Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, 210029, Jiangsu, China.

Molecular Biology Reports
|October 9, 2020
PubMed

Insights

Kruppel-like factor 5 (KLF5) upregulates AarF domain containing kinase 4 (ADCK4) in nephrotic syndrome (NS) podocyte disease. KLF5 binds to the ADCK4 promoter, increasing its transcriptional activity and expression.

Area of Science:

  • Molecular Biology
  • Genetics
  • Nephrology

Background:

  • AarF domain containing kinase 4 (ADCK4) and Kruppel-like factor 5 (KLF5) are implicated in podocyte disease.
  • The precise interaction between ADCK4 and KLF5 in nephrotic syndrome (NS) pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the regulatory relationship between KLF5 and ADCK4 in the context of NS.
  • To determine if KLF5 influences ADCK4 expression and activity.

Main Methods:

  • Analysis of ADCK4 and KLF5 mRNA levels in NS patients.
  • Cloning and functional analysis of the ADCK4 promoter region using deletion and mutation studies in cell lines (Hela, A549, HEK 293).
  • Chromatin immunoprecipitation (ChIP) assay to confirm KLF5 binding to the ADCK4 promoter.

Main Results:

  • ADCK4 and KLF5 mRNA levels were decreased and linearly correlated in NS patients.
  • Deletion analysis identified a core ADCK4 promoter region (-116/-4 relative to TSS).
  • KLF5 binding sites within the ADCK4 promoter were critical for its activity, with KLF5 upregulating ADCK4 mRNA and protein levels in HEK293 cells. ChIP confirmed KLF5 binding to the ADCK4 promoter.

Conclusions:

  • KLF5 positively regulates the transcriptional activity of ADCK4.
  • This interaction suggests a novel molecular mechanism in the development of podocyte disease and nephrotic syndrome.
Keywords:
AarF domain containing kinase 4Kruppel-like factor 5Nephrotic syndromePromoterTranscriptional regulation

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