KLF14 Inhibits Renal Mesangial Cell Proliferation by Promoting Btg2 Gene Expression
Abstract Krüppel-like factor 14 is one of zinc finger protein family that are closely associated with regulation of transcription, and its function in the kidneys remains unclear. So KLF14-deficient mouse models were established using TALEN. The levels of blood cholesterol, HDL-C, LDL-C, and TGs were significantly decreased in KLF14-/- mice. KLF14-/- mice had more obvious mesangial cell proliferation and greater accumulation of extracellular matrix. RNA-Seq showed that these differentially expressed genes were mainly involved in metabolism, proliferation and inflammation pathways. ChIP-Seq was performed to identify KLF14 target genes. Five overlapping KLF14 target genes (Btg2, Socs2, Hdc, Ler2 and Akr1b3) were identified by combined analyses of RNA-Seq and ChIP-SEq. Dual luciferase reporter assay and EMSA confirmed that Btg2 was a target gene of KLF14. EdU assay revealed that KLF14 could inhibit the proliferation of primary renal mesangial cells by promoting Btg2 expression. KLF14 might exert its function in kidneys by regulating metabolism, proliferation, and inflammation signaling pathways. KLF14 inhibited the proliferation of primary RMCs by promoting expression of its target gene Btg2. This study provides a basis for further functional studies of KLF14 in the development of kidney diseases, especially in mesangial proliferative glomerulonephritis, metabolic nephropathy and kidney tumors.