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Abstract: TH-PO798

KLF15 Suppress Mesangial Cell Proliferation via Increasing the Sumoylation of P53

Session Information

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix


  • Hong, Quan, Chinese PLA Genaral Hospital, Beijing, BEIJING, China
  • Li, Ou, Chinese PLA Genaral Hospital, Beijing, BEIJING, China
  • Cai, Guangyan, Chinese PLA Genaral Hospital, Beijing, BEIJING, China
  • Chen, Xiangmei, Chinese PLA Genaral Hospital, Beijing, BEIJING, China

Mesangial cell proliferation is a key pathological feature in a number of common human renal diseases including IgA and diabetic nephropathies. Knowledge of MCs response to pathological stimuli is crucial to the understanding of these disease processes. Our previous study demonstrated Krüppel-like factor 15 (KLF15), a kidney-enriched zinc finger transcription factor, is required for inhibiting the proliferation of mesangial cell. This study aims to clarify the direct target gene and the downstream mechanism of KLF15 regulating mesangial proliferation.


DNA of primary human glomeruli mesangial cells (HMCs) was purified for sequencing after the chromatin immunoprecipitation with anti-KLF15 antibody. Differential expression protein of cells overexpressed KLF15 were assayed by SILAC/HPLC/MS-MS. We screened out small ubiquitin-related modifier 1 (SUMO1) as the direct transcriptional target of KLF15 and validated with ChIP-PCR or Luciferase assay. Finally, we interpreted whether SUMO1 was able to sumolyate p53 then block cell cycle and inhibit cell proliferation using co-IP and EDU assay in vitro. Also demonstrated these mechanisms on the anti-thy1 rat model.


We showed that in vitro treatment with PDGF BB or high glucose induced a rapid decrease of KLF15 and SUMO1 expression in HMC with proliferation, also decreased in the renal cortex of anti-thy 1 model at the proliferated periods. SUMO1 was screened out and validated as one of the direct target proteins of KLF15. SUMOs are a group of post-translational modification proteins and participate in transcriptional regulation, protein stabilization, and the cell cycle. Furthermore we demonstrated overexpress KLF15 or SUMO1 enhanced the stability of P53 (Sumolyation-p53 expression increased) that functioned to block the cell cycle of HMCs, therefore obliterate the cell proliferation. Conversely, knockdown of SUMO1, even if cultured with PDGF BB, HMCs proliferation rates declined along with less sumolyation-P53. Finally, results showed the level of sumolyation-P53 in the kidney cortex from anti-thy 1 rat model decreased at proliferation periods.


These studies manipulate the critical mechanism of KLF15 targeting SUMO1 in mediating the proliferation of mesangial cells. It will be a potential target for IgAN or diabetic nephropahty's therapy.