2. Academic Validation
  3. FKN secreted by kidney epithelial cells regulates macrophage activation in lupus nephritis via the Hippo signaling pathway

FKN secreted by kidney epithelial cells regulates macrophage activation in lupus nephritis via the Hippo signaling pathway

  • Lupus. 2023 Sep 26:9612033231204068. doi: 10.1177/09612033231204068.
Yao Zuo 1 2,  Xiuhong Pan 2,  Xiaochao Wang 2,  Yanwu You 3
Affiliations

Affiliations

  • 1 First Affiliated Hospital of Jinan University, Guangzhou, China.
  • 2 Department of Hematology & Oncology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
  • 3 Department of Nephrology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
PMID: 37751892 DOI: 10.1177/09612033231204068
Abstract

Background: Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE), and its pathogenesis is not fully understood. Previously, we showed that fractalkine (FKN) expression was positively correlated with the severity of LN. Here, we aimed to study the role of the Hippo signaling pathway (HSP) and its interaction with FKN in LN in an attempt to provide novel strategies for LN treatment.

Methods: In this study, lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-stimulated THP-1 cells were co-cultured with FKN up-regulated or down-regulated kidney epithelial cells Hkb20. FKN-knockout (KO-FKN) mice were used to construct LN model. Flow cytometric analysis, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), pathological staining, Western blot, and immunofluorescence (IF) staining were employed to investigate the role of FKN and its interaction with the Hippo signaling pathway (HSP) in LN.

Results: Up-regulation of FKN in kidney epithelial cells was associated with increased macrophage activation. FKN overexpression in kidney epithelial cells suppressed Apoptosis, inflammation levels, and M1 polarization of THP-1 cells and inhibited the HSP. Oppositely, FKN knockdown in kidney epithelial cells increased Apoptosis, inflammation, and M1 polarization and activated the HSP. HSP Inhibitor reversed the effect of FKN knockdown on THP-1 cells. In LN mice, FKN knockout and YAP Inhibitor decreased the levels of renal function markers, alleviated kidney injury induced by LN, and inhibited macrophage activation in LN mice.

Conclusions: FKN down-regulation reduced the activation of macrophages in renal tissue and alleviated kidney damage by activating HSP. The regulatory effect of FKN on HSP should be confirmed in patients with LN, and the mechanism of FKN in LN should be further explored.

Keywords

Hippo signaling pathway; Lupus nephritis; fractalkine; macrophage; polarization.

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