Pharmacological inhibition of SETD7 by PFI-2 attenuates renal fibrosis following folic acid and obstruction injury

  • Eur J Pharmacol. 2021 Jun 15;901:174097. doi: 10.1016/j.ejphar.2021.174097.
Benquan Liu  1 ,  Jiayi Nie  1 ,  Hua Liang  2 ,  Zijie Liang  3 ,  Jiangju Huang  1 ,  Wenqiang Yu  1 ,  Shihong Wen  4
Affiliations
  • 1. Department of Anesthesiology, The First People's Hospital of Foshan, Foshan, 528000, China.
  • 2. Department of Anesthesiology, The First People's Hospital of Foshan, Foshan, 528000, China; Translational Medicine Institute of Anesthesiology and Perioperative Medicine, The First People's Hospital of Foshan, Foshan, 528000, China. Electronic address: [email protected].
  • 3. Department of Nephrology, The First People's Hospital of Foshan, Foshan, 528000, China.
  • 4. Department of Anesthesiology, The First Affiliated Hospital of SUN YAT-SEN University, Guangzhou, 510080, China.
PMID: 33848540 DOI: 10.1016/j.ejphar.2021.174097
Abstract

Renal fibrosis is the common pathological hallmark of chronic kidney disease, and SET domain containing lysine methyltransferase 7 (SETD7) promote considerably renal fibrosis. However, the signaling mechanisms underlying SETD7 driving renal fibrosis are not fully understood. Here, we investigated the role of SETD7 in M2 macrophages-myofibroblasts transition and the myeloid fibroblasts activation in folic acid and obstruction-induced renal fibrosis. Mice treated with PFI-2, an inhibitor of SETD7, presented less bone marrow-derived myofibroblasts, fewer CD206+/α-smooth muscle actin + cells and developed less renal fibrosis (P＜0.01). Furthermore, SETD7 inhibition reduced the infiltration of inflammatory cells and decreased the production of pro-inflammatory cytokines and chemokines in the kidneys after folic acid treatment (P＜0.01). Finally, SETD7 inhibition suppressed the accumulation of NF-κB p65+ cells in folic acid nephropathy (P＜0.01). Taken together, SETD7 mediates M2 macrophages-myofibroblasts transition, bone marrow-derived myofibroblasts activation, and inflammation response in the development of renal fibrosis.

Keywords
Inflammation; Macrophage; Renal fibrosis; SETD7.
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