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Alpha1-Antitrypsin Attenuates Renal Fibrosis by Inhibiting TGF-ß1-Induced Epithelial Mesenchymal Transition.
Cho, Jang-Hee; Ryu, Hye-Myung; Oh, Eun-Joo; Yook, Ju-Min; Ahn, Ji-Sun; Jung, Hee-Yeon; Choi, Ji-Young; Park, Sun-Hee; Kim, Yong-Lim; Kwak, Ihm Soo; Kim, Chan-Duck.
Afiliación
  • Cho JH; Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
  • Ryu HM; Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
  • Oh EJ; Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
  • Yook JM; Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
  • Ahn JS; Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
  • Jung HY; Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
  • Choi JY; Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
  • Park SH; Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
  • Kim YL; Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
  • Kwak IS; Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.
  • Kim CD; Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
PLoS One ; 11(9): e0162186, 2016.
Article en En | MEDLINE | ID: mdl-27607429
Alpha1-antitrypsin (AAT) exerts its anti-inflammatory effect through regulating the activity of serine proteinases. This study evaluated the inhibitory effects of AAT against the transforming growth factor (TGF)-ß1 induced epithelial-to-mesenchymal transition (EMT) in unilateral ureter obstruction (UUO) mice and Madin-Darby canine kidney (MDCK) cells. C57BL/6 mice with induced UUO were injected intraperitoneally with AAT (80 mg/Kg) or vehicle for 7 days. MDCK cells were treated with TGF-ß1 (2 ng/mL) for 48 hours to induce EMT, and co-treated with AAT (10 mg/mL) to inhibit the EMT. Masson's trichrome and Sirius red staining was used to estimate the extent of renal fibrosis in UUO mice. The expression of alpha-smooth muscle actin (α-SMA), vimentin, fibronectin, collagen I, and E-cadherin in MDCK cells and kidney tissue were evaluated. Masson's and Sirius red staining revealed that the area of renal fibrosis was significantly smaller in AAT treated UUO group compared with that of UUO and vehicle treated UUO groups. AAT treatment attenuated upregulation of Smad2/3 phosphorylation in UUO mouse model. Co-treatment of MDCK cells with TGF-ß1 and AAT significantly attenuated the changes in the expression of α-SMA, vimentin, fibronectin, collagen I, and E-cadherin. AAT also decreased the phosphorylated Smad3 expression and the phosphorylated Smad3/Smad3 ratio in MDCK cells. AAT treatment inhibited EMT induced by TGF-ß1 in MDCK cells and attenuated renal fibrosis in the UUO mouse model. The results of this work suggest that AAT could inhibit the process of EMT through the suppression of TGF-ß/Smad3 signaling.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Alfa 1-Antitripsina / Factor de Crecimiento Transformador beta1 / Transición Epitelial-Mesenquimal / Riñón Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Alfa 1-Antitripsina / Factor de Crecimiento Transformador beta1 / Transición Epitelial-Mesenquimal / Riñón Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos