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  • Krϋppel-like factor 15 suppresses renal glomerular mesangial cell proliferation via enhancing P53 SUMO1 conjugation.

Krϋppel-like factor 15 suppresses renal glomerular mesangial cell proliferation via enhancing P53 SUMO1 conjugation.

Journal of cellular and molecular medicine (2021-05-06)
Lingling Wu, Ou Li, Fengge Zhu, Xu Wang, Pu Chen, Guangyan Cai, Xiangmei Chen, Quan Hong
ABSTRACT

Mesangial cell (MC) proliferation is a key pathological feature in a number of common human renal diseases, including mesangial proliferative nephritis and diabetic nephropathies. Knowledge of MC responses to pathological stimuli is crucial to the understanding of these disease processes. We previously determined that Krϋppel-like factor 15 (KLF15), a kidney-enriched zinc-finger transcription factor, was required for inhibition of MC proliferation. In the present study, we investigated the direct target gene and the underlying mechanism by which KLF15 regulated mesangial proliferation. First, we screened small ubiquitin-related modifier 1 (SUMO1) as the direct transcriptional target of KLF15 and validated this finding with ChIP-PCR and luciferase assays. Furthermore, we demonstrated that overexpressing KLF15 or SUMO1 enhanced the stability of P53, which blocked the cell cycle of human renal MCs (HRMCs) and therefore abolished cell proliferation. Conversely, knockdown of SUMO1 in HRMCs, even those overexpressed with KLF15, could not inhibit HRMC proliferation rates and increase SUMOylation of P53. Finally, the results showed that the levels of SUMOylated P53 in the kidney cortices of anti-Thy 1 model rats were decreased during proliferation periods. These findings reveal the critical mechanism by which KLF15 targets SUMO1 to mediate the proliferation of MCs.

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Sigma-Aldrich
Anti-actinaβ monoclonale, clone AC-74, ascites fluid
Sigma-Aldrich
Anti-p53 antibody, Mouse monoclonal, clone BP53-12, ascites fluid
Sigma-Aldrich
Anti-KLF15 antibody produced in rabbit, IgG fraction of antiserum
Sigma-Aldrich
Anti-SUMO-1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution