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Deletion of p38 MAPK in macrophages ameliorates peritoneal fibrosis and inflammation in peritoneal dialysis.
Ikushima, Akie; Ishimura, Takuya; Mori, Keita P; Yamada, Hiroyuki; Sugioka, Sayaka; Ishii, Akira; Toda, Naohiro; Ohno, Shoko; Kato, Yukiko; Handa, Takaya; Yanagita, Motoko; Yokoi, Hideki.
Afiliación
  • Ikushima A; Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Kyoto, 6068507, Japan.
  • Ishimura T; Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Kyoto, 6068507, Japan.
  • Mori KP; Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Kyoto, 6068507, Japan.
  • Yamada H; Department of Nephrology and Dialysis, Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-Kofukai, Osaka, Japan.
  • Sugioka S; Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Kyoto, 6068507, Japan.
  • Ishii A; Department of Primary Care & Emergency Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Toda N; Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Kyoto, 6068507, Japan.
  • Ohno S; Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Kyoto, 6068507, Japan.
  • Kato Y; Department of Nephrology, Kansai Electric Power Hospital, Osaka, Japan.
  • Handa T; Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Kyoto, 6068507, Japan.
  • Yanagita M; Department of Nephrology, Kansai Electric Power Hospital, Osaka, Japan.
  • Yokoi H; Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Kyoto, 6068507, Japan.
Sci Rep ; 14(1): 21220, 2024 09 11.
Article en En | MEDLINE | ID: mdl-39261560
ABSTRACT
One of the most common causes of peritoneal dialysis withdrawal is ultrafiltration failure which is characterized by peritoneal membrane thickening and fibrosis. Although previous studies have demonstrated the inhibitory effect of p38 MAPK inhibitors on peritoneal fibrosis in mice, it was unclear which specific cells contribute to peritoneal fibrosis. To investigate the role of p38 MAPK in peritoneal fibrosis more precisely, we examined the expression of p38 MAPK in human peritoneum and generated systemic inducible p38 MAPK knockout mice and macrophage-specific p38 MAPK knockout mice. Furthermore, the response to lipopolysaccharide (LPS) was assessed in p38 MAPK-knocked down RAW 264.7 cells to further explore the role of p38 MAPK in macrophages. We found that phosphorylated p38 MAPK levels were increased in the thickened peritoneum of both human and mice. Both chlorhexidine gluconate (CG)-treated systemic inducible and macrophage-specific p38 MAPK knockout mice ameliorated peritoneal thickening, mRNA expression related to inflammation and fibrosis, and the number of αSMA- and MAC-2-positive cells in the peritoneum compared to CG control mice. Reduction of p38 MAPK in RAW 264.7 cells suppressed inflammatory mRNA expression induced by LPS. These findings suggest that p38 MAPK in macrophages plays a critical role in peritoneal inflammation and thickening.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diálisis Peritoneal / Proteínas Quinasas p38 Activadas por Mitógenos / Fibrosis Peritoneal / Inflamación / Macrófagos Límite: Animals / Humans / Male Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diálisis Peritoneal / Proteínas Quinasas p38 Activadas por Mitógenos / Fibrosis Peritoneal / Inflamación / Macrófagos Límite: Animals / Humans / Male Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido