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Emodin suppresses mast cell migration via modulating the JAK2/STAT3/JMJD3/CXCR3 signaling to prevent cystitis.
Xin, Ke; Ge, Manqing; Li, Xukun; Su, Hongwei; Ke, Jingwei; Chen, Kaifa; Tang, Yiquan; Wang, Yinghong; Lai, Junyu.
Afiliación
  • Xin K; Department of Urology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
  • Ge M; Department of Anorectal Surgery, The Affiliated TCM Hospital of Southwest Medical University, Luzhou, Sichuan, China.
  • Li X; Department of Urology, The Affiliated TCM Hospital of Southwest Medical University, Luzhou, Sichuan, China.
  • Su H; Department of Urology, The Affiliated TCM Hospital of Southwest Medical University, Luzhou, Sichuan, China.
  • Ke J; Department of Urology, The Affiliated TCM Hospital of Southwest Medical University, Luzhou, Sichuan, China.
  • Chen K; Department of Urology, The Affiliated TCM Hospital of Southwest Medical University, Luzhou, Sichuan, China.
  • Tang Y; Department of Urology, The Affiliated TCM Hospital of Southwest Medical University, Luzhou, Sichuan, China.
  • Wang Y; Department of Urology, The Affiliated TCM Hospital of Southwest Medical University, Luzhou, Sichuan, China.
  • Lai J; Department of Urology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Neurourol Urodyn ; 43(8): 2258-2268, 2024 Nov.
Article en En | MEDLINE | ID: mdl-38979835
ABSTRACT

AIMS:

This study aimed to determine the preventive effects of emodin on cyclophosphamide (CYP)-induced cystitis and to explore the molecular mechanism.

METHODS:

In vivo, mice were modeled by CYP. Before a half hour of CYP treatment, Jumonji domain-containing protein-3 (JMJD3) inhibitors (GSK-J4) and emodin were used to treat CYP model mice. Bladder samples were stained for hematoxylin-eosin and toluidine blue. Next, JMJD3 was quantified by immunofluorescence staining, RT-PCR, and Western blot. CXCR3 was quantified by Western blot and ELISA. In vitro, before stimulated by lipopolysaccharide (LPS), human bladder smooth muscle cells (hBSMCs) were transfected with pcDNA3.1-JMJD3 plasmids, shRNA-JMJD3 plasmids or pretreated with emodin. Collected cells to detect JMJD3 and CXCR3 ligands again; collected supernatant of culture for Transwell assay. Finally, as the JAK2 inhibitor, AG490 was used to pretreat LPS-induced hBSMCs. Western blot was performed to quantify proteins.

RESULTS:

Emodin inhibited mast cell migration and suppressed the expression of JMJD3, CXCR3, and CXCR3 ligands, not only in vivo but also in vitro. The pharmacological effects of emodin were similar to GSK-J4 or JMJD3 inhibition. In addition, emodin significantly downregulated the phosphorylation of JAK2 and STAT3, and inhibited JMJD3/CXCR3 axis transduction like AG490.

CONCLUSION:

Emodin has a preventive effect on cystitis by inhibiting mast cell migration through inhibition of the JAK2/STAT3/JMJD3/CXCR3 signaling pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Movimiento Celular / Emodina / Cistitis / Factor de Transcripción STAT3 / Janus Quinasa 2 / Receptores CXCR3 / Mastocitos Límite: Animals / Female / Humans Idioma: En Revista: Neurourol Urodyn Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Movimiento Celular / Emodina / Cistitis / Factor de Transcripción STAT3 / Janus Quinasa 2 / Receptores CXCR3 / Mastocitos Límite: Animals / Female / Humans Idioma: En Revista: Neurourol Urodyn Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos