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Formononetin Alleviates Ischemic Acute Kidney Injury by Regulating Macrophage Polarization through KLF6/STAT3 Pathway.
Zhang, Ning-Xin; Guan, Chen; Li, Chen-Yu; Xu, Ling-Yu; Xin, Yan-Lu; Song, Zhuo; Li, Tian-Yang; Yang, Cheng-Yu; Zhao, Long; Che, Lin; Wang, Yan-Fei; Man, Xiao-Fei; Xu, Yan.
Afiliación
  • Zhang NX; Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Guan C; Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Li CY; Medizinische Klinik und Poliklinik IV, Klinikum der Universität, LMU München, München, Germany.
  • Xu LY; Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Xin YL; Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Song Z; Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Li TY; Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Yang CY; Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Zhao L; Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Che L; Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Wang YF; Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Man XF; Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Xu Y; Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Am J Chin Med ; : 1-19, 2024 Aug 22.
Article en En | MEDLINE | ID: mdl-39169449
ABSTRACT
Recent research has indicated that formononetin demonstrates a potent anti-inflammatory effect in various diseases. However, its impact on sterile inflammation kidney injury, specifically acute kidney injury (AKI), remains unclear. In this study, we utilized an ischemia/reperfusion-induced AKI (IRI-AKI) mouse model and bone marrow-derived macrophages (BMDMs) to investigate the effects of formononetin on sterile inflammation of AKI and to explore the underlying mechanism. The administration of formononetin significantly preserved kidney function from injury, as evidenced by lower serum creatinine and blood urea nitrogen levels compared to IRI-AKI mice without treatment. This was further confirmed by less pathological changes in renal tubules and low expression of tubular injury markers such as KIM-1 and NGAL in the formononetin-treated IRI-AKI group. Furthermore, formononetin effectively suppressed the expression of pro-inflammatory cytokines (MCP-1, TNF-[Formula see text], and IL-1[Formula see text]) and macrophage infiltration into the kidneys of AKI mice. In vitro studies showed that formononetin led to less macrophage polarization towards a pro-inflammatory phenotype in BMDMs stimulated by LPS and IFN-[Formula see text]. The mechanism involved the KLF6 and p-STAT3 pathway, as overexpression of KLF6 restored pro-inflammatory cytokine levels and pro-inflammatory polarization. Our findings demonstrate that formononetin can significantly improve renal function and reduce inflammation in IRI-AKI, which may be attributed to the inhibition of KLF6/STAT3-mediated macrophage pro-inflammatory polarization. This discovery presents a new promising therapeutic option for the treatment of IRI-AKI.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Am J Chin Med Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Singapur
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Am J Chin Med Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Singapur