Ranunculus ternatus Thunb extract attenuates renal fibrosis of diabetic nephropathy via inhibiting SMYD2.
Ranunculus ternatus Thunb extract attenuates renal fibrosis of diabetic nephropathy via inhibiting SMYD2.
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毛茛提取物通过抑制 SMYD2 减轻糖尿病肾病的肾纤维化
DOI：
10.1080/13880209.2022.2030759
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发表时间：
2022-12
影响因子：
3.8
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Xu W;Peng R;Chen S;Wu C;Wang X;Yu T;Jian J;Zhang N;Zuo S;Chen M;Guo B;Liu L
毛茛（Ranunculus ternatus Thunb）（毛茛科）（RTT）在临床上用于治疗结核病或作为肿瘤辅助治疗，但其对糖尿病肾病（DN）的潜在作用尚未研究。目的：探讨雷公藤多甙提取物对糖尿病肾病肾纤维化的影响。将C57 BL/6小鼠随机分为4组（n = 12）。用链脲佐菌素（STZ，55 mg/kg/d）连续5天诱导糖尿病（DM）小鼠，并用RTT提取物（2g/kg）治疗。然后测定血糖、HE及Masson染色。Western blot检测Vimentin、α-SMA、TNF-α、NF-κB p-p65、NF-κB p65、SMYD 2、H3 K36 me 3、H3 K4 me 3的表达水平。纤维连接蛋白分别用免疫印迹法和免疫荧光染色法检测。RTT提取物能明显减轻糖尿病小鼠肾组织纤维连接蛋白（Fibronectin，FN）、波形蛋白（Vimentin，Vimentin）和α-SMA的表达（分别为65%、75%和53%）。此外，DN小鼠TNF-α（57%）、NF-κB p-p65和NF-κB p65（35%和25%）水平升高。重要的是，这些在RTT提取物治疗后得到缓解。此外，我们观察到用RTT提取物治疗后，DN小鼠中SMYD 2（30%）、H3 K36 me 3和H3 K4 me 3（53%和75%）的蛋白水平降低。RTT提取物主要通过抑制SMYD 2活化和H3 K36 me 3和H3 K4 me 3蛋白表达来介导STZ诱导的DN的抗纤维化和抗炎反应。RTT提取物可能对高糖诱导的肾病具有治疗潜力。
Ranunculus ternatus Thunb (Ranunculaceae), (RTT) is used clinically for the treatment of tuberculosis or as tumour adjuvant therapy, but its potential effect on diabetic nephropathy (DN) has not been studied. To investigate the effect of RTT extract in renal fibrosis of DN. C57BL/6 mice were randomly divided into four groups (n = 12). Diabetes mellitus (DM) mice were induced by streptozotocin (STZ, 55 mg/kg/day) for five consecutive days and treated by RTT extract (2 g/kg). Afterward, blood glucose, HE and Masson staining were assayed. The expression levels of Vimentin, ɑ-SMA, TNF-ɑ, NF-κB p-p65, NF-κB p65, SMYD2, H3K36me3, H3K4me3 were determined by western blots. Firbronectin was respectively assayed by western blot and immunofluorescent staining. RTT extract significantly ameliorated renal injury and renal fibrosis in the renal tissue of STZ-induced diabetic mice as demonstrated by the decreased expression level of Fibronectin (65%), Vimentin and α-SMA (75% & 53%). In addition, the levels of TNF-α (57%), NF-κB p-p65 and NF-κB p65 (35% & 25%) were elevated in the DN mice. Importantly, these were alleviated after RTT extract treatment. Moreover, we observed that the protein levels of SMYD2 (30%), H3K36me3 and H3K4me3 (53% & 75%) were reduced in DN mice after treatment with RTT extract. RTT extract mediates antifibrotic effects and anti-inflammatory responses in STZ-induced DN mainly through suppressing SMYD2 activation and H3K36me3 and H3K4me3 protein expression. RTT extract might have therapeutic potential against high glucose-induced nephropathy.
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影响因子：
2.6
作者：
Hao DC;He CN;Shen J;Xiao PG
通讯作者：
Xiao PG
NF-κB：通过甲基化调节。
影响因子：
11.2
作者：
Lu T;Stark GR
通讯作者：
Stark GR
影响因子：
5.1
作者：
Cho, N. H.;Shaw, J. E.;Malanda, B.
通讯作者：
Malanda, B.
影响因子：
2
作者：
Li, Ming;Li, Can-ming;Lou, Tan-qi
通讯作者：
Lou, Tan-qi
DOI：
10.1152/ajprenal.00393.2016
发表时间：
2017-08-01
影响因子：
4.2
作者：
Malik, Salma;Suchal, Kapil;Arya, Dharamvir Singh
通讯作者：
Arya, Dharamvir Singh