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TGF-β1 suppresses CCL3/4 expression through the ERK signaling pathway and inhibits intervertebral disc degeneration and inflammation-related pain in a rat model
Experimental & Molecular Medicine ; : e379-2017.
Artículo en Inglés | WPRIM | ID: wpr-127722
ABSTRACT
The objective of this study was to investigate the regulatory effects of TGF-β1 on CCL3/4 expression and inflammation-related pain during intervertebral disc degeneration (IVDD). TGF-β1 and CCL3/4 expression patterns in different degenerative human nucleus pulposus (NP) tissues were measured by qPCR and immunohistochemistry (IHC), and the effects of TGF-β1 on CCL3/4 expression were measured by qPCR, ELISA and immunofluorescence. The roles of NF-κB and MAPK in TGF-β1-mediated CCL3/4 promoter activity were studied using siRNAs, western blotting and qPCR. After establishing an IVDD rat model in vivo, we administered intradiscal injections of TGF-β1. The effects of TGF-β1 on IVDD were determined by MRI and histological analyses, and the effects of TGF-β1 on dorsal root ganglion (DRG) inflammation and pain development were determined by IHC staining and pain-behavior testing, respectively. TGF-β1 and CCL3/4 expression was elevated in degenerative NP tissue. CCL4 expression was significantly inhibited by TGF-β1 treatment. Pharmacological inhibition or siRNA knockdown of the ERK1/2 signaling attenuated TGF-β1-mediated suppression of CCL4 expression. In vivo, TGF-β1 injection inhibited the development of degenerative features in the IVDD model. Moreover, TGF-β1 prevented the inflammatory response and pain development. The results of this study show that TGF-β1 downregulates CCL4 expression through ERK1/2 signaling activation in NP cells. Furthermore, TGF-β1 can prevent degenerative processes, inhibit inflammatory responses in the DRG and prevent pain development in the IVDD rat model. The results of this study indicate that TGF-β1 may represent a therapeutic target for the control of inflammation-related pain associated with IVDD.
Asunto(s)
Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Ensayo de Inmunoadsorción Enzimática / Inmunohistoquímica / Imagen por Resonancia Magnética / Western Blotting / Técnica del Anticuerpo Fluorescente / Grupos Diagnósticos Relacionados / Modelos Animales / ARN Interferente Pequeño / Degeneración del Disco Intervertebral / Ganglios Espinales Límite: Animales / Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2017 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Ensayo de Inmunoadsorción Enzimática / Inmunohistoquímica / Imagen por Resonancia Magnética / Western Blotting / Técnica del Anticuerpo Fluorescente / Grupos Diagnósticos Relacionados / Modelos Animales / ARN Interferente Pequeño / Degeneración del Disco Intervertebral / Ganglios Espinales Límite: Animales / Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2017 Tipo del documento: Artículo