Tags

Type your tag names separated by a space and hit enter

Alpha1-Antitrypsin Attenuates Renal Fibrosis by Inhibiting TGF-β1-Induced Epithelial Mesenchymal Transition.
PLoS One. 2016; 11(9):e0162186.Plos

Abstract

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)-β1 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-β1 (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-β1 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-β1 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-β/Smad3 signaling.

Authors+Show Affiliations

Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27607429

Citation

Cho, Jang-Hee, et al. "Alpha1-Antitrypsin Attenuates Renal Fibrosis By Inhibiting TGF-β1-Induced Epithelial Mesenchymal Transition." PloS One, vol. 11, no. 9, 2016, pp. e0162186.
Cho JH, Ryu HM, Oh EJ, et al. Alpha1-Antitrypsin Attenuates Renal Fibrosis by Inhibiting TGF-β1-Induced Epithelial Mesenchymal Transition. PLoS One. 2016;11(9):e0162186.
Cho, J. H., Ryu, H. M., Oh, E. J., Yook, J. M., Ahn, J. S., Jung, H. Y., Choi, J. Y., Park, S. H., Kim, Y. L., Kwak, I. S., & Kim, C. D. (2016). Alpha1-Antitrypsin Attenuates Renal Fibrosis by Inhibiting TGF-β1-Induced Epithelial Mesenchymal Transition. PloS One, 11(9), e0162186. https://doi.org/10.1371/journal.pone.0162186
Cho JH, et al. Alpha1-Antitrypsin Attenuates Renal Fibrosis By Inhibiting TGF-β1-Induced Epithelial Mesenchymal Transition. PLoS One. 2016;11(9):e0162186. PubMed PMID: 27607429.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alpha1-Antitrypsin Attenuates Renal Fibrosis by Inhibiting TGF-β1-Induced Epithelial Mesenchymal Transition. AU - Cho,Jang-Hee, AU - Ryu,Hye-Myung, AU - Oh,Eun-Joo, AU - Yook,Ju-Min, AU - Ahn,Ji-Sun, AU - Jung,Hee-Yeon, AU - Choi,Ji-Young, AU - Park,Sun-Hee, AU - Kim,Yong-Lim, AU - Kwak,Ihm Soo, AU - Kim,Chan-Duck, Y1 - 2016/09/08/ PY - 2016/04/27/received PY - 2016/08/18/accepted PY - 2016/9/9/entrez PY - 2016/9/9/pubmed PY - 2017/8/5/medline SP - e0162186 EP - e0162186 JF - PloS one JO - PLoS One VL - 11 IS - 9 N2 - 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)-β1 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-β1 (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-β1 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-β1 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-β/Smad3 signaling. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/27607429/Alpha1_Antitrypsin_Attenuates_Renal_Fibrosis_by_Inhibiting_TGF_β1_Induced_Epithelial_Mesenchymal_Transition_ L2 - https://dx.plos.org/10.1371/journal.pone.0162186 DB - PRIME DP - Unbound Medicine ER -