Alpha1-Antitrypsin Attenuates Renal Fibrosis by Inhibiting TGF-β1-Induced Epithelial Mesenchymal Transition.
Alpha1-Antitrypsin Attenuates Renal Fibrosis by Inhibiting TGF-β1-Induced Epithelial Mesenchymal Transition.
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Alpha1-抗胰蛋白酶通过抑制TGF-β1诱导的上皮间质转变来减轻肾纤维化。
DOI：
10.1371/journal.pone.0162186
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kim CD
中科院分区：
文献类型：
--
作者：
Cho JH;Ryu HM;Oh EJ;Yook JM;Ahn JS;Jung HY;Choi JY;Park SH;Kim YL;Kwak IS;Kim CD
α 1-抗胰蛋白酶（AAT）通过调节丝氨酸蛋白酶的活性发挥其抗炎作用。本研究观察了AAT对转化生长因子（TGF）-β1诱导的单侧输尿管梗阻（UUO）小鼠和犬肾（MDCK）细胞上皮-间质转化（EMT）的抑制作用。用AAT（80 mg/Kg）或媒介物腹膜内注射具有诱导的UUO的C57 BL/6小鼠7天。用TGF-β1（2 ng/mL）处理MDCK细胞48小时以诱导EMT，并用AAT（10 mg/mL）共处理以抑制EMT。Masson三色染色和天狼星红染色用于估计UUO小鼠中肾纤维化的程度。检测MDCK细胞和肾组织中α-平滑肌肌动蛋白（α-SMA）、波形蛋白、纤连蛋白、I型胶原和E-钙粘蛋白的表达。Masson和天狼星红染色显示，与UUO和溶剂处理的UUO组相比，AAT处理的UUO组的肾纤维化面积显著较小。AAT处理减弱UUO小鼠模型中Smad 2/3磷酸化的上调。TGF-β1和AAT共同处理MDCK细胞可显著减弱α-SMA、波形蛋白、纤维连接蛋白、I型胶原和E-钙粘蛋白表达的变化。AAT还可降低MDCK细胞中磷酸化Smad 3的表达和磷酸化Smad 3/Smad 3比值。AAT治疗抑制MDCK细胞中TGF-β1诱导的EMT，并减轻UUO小鼠模型中的肾纤维化。本研究结果提示，AAT可能通过抑制TGF-β/Smad 3信号通路而抑制EMT的发生。
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.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3.5
作者：
BUCURENCI, N;BLAKE, DR;WINYARD, PG
通讯作者：
WINYARD, PG
DOI：
10.1152/ajprenal.2001.280.5.f777
发表时间：
2001-05-01
影响因子：
4.2
作者：
Guo, GJ;Morrissey, J;Klahr, S
通讯作者：
Klahr, S
影响因子：
13.6
作者：
Park, Sun-Hee;Choi, Min-Jeong;Kim, Yong-Lim
通讯作者：
Kim, Yong-Lim
影响因子：
13.6
作者：
Ai, Jun;Nie, Jing;Hou, Fan Fan
通讯作者：
Hou, Fan Fan