Leptin downregulates aggrecan through the p38-ADAMST pathway in human nucleus pulposus cells.
Leptin downregulates aggrecan through the p38-ADAMST pathway in human nucleus pulposus cells.
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瘦素通过人髓核细胞中的 p38-ADAMST 途径下调聚集蛋白聚糖
DOI：
10.1371/journal.pone.0109595
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Shen J
中科院分区：
文献类型：
--
作者：
Li Z;Yu X;Liang J;Wu WK;Yu J;Shen J
肥胖相关的椎间盘退变（IDD）的机制基础尚不清楚。聚集蛋白聚糖及其降解酶ADAMTS-4和ADAMTS-5的异常表达与IDD的发生有关。在这里，我们研究了瘦素，一种在肥胖症中循环水平增加的激素，对原代人髓核（NP）细胞中聚集蛋白聚糖和ADAMTS表达的影响。Real-time PCR和Western blot结果显示，瘦素可显著上调NP细胞ADAMTS-4和ADAMTS-5的mRNA和蛋白表达，降低NP细胞聚集蛋白聚糖的水平，并显著诱导p38磷酸化。用SB 203580（一种p38抑制剂）处理NP细胞可阻断瘦素对聚集蛋白聚糖和ADAMTS的调节。通过siRNA敲低ADAMTS-4和ADAMTS-5也减弱了瘦素刺激的NP细胞中聚集蛋白聚糖的降解。总之，我们证明了瘦素诱导p38上调ADAMTS，从而促进人NP细胞中聚集蛋白聚糖的降解。这些结果为肥胖相关IDD的分子发病机制提供了新的机制见解。
The mechanistic basis of obesity-associated intervertebral disc degeneration (IDD) is unclear. Aberrant expression of aggrecan and its degrading enzymes ADAMTS-4 and ADAMTS-5 is implicated in the development of IDD. Here, we investigated the effect of leptin, a hormone with increased circulating levels in obesity, on the expression of aggrecan and ADAMTSs in primary human nucleus pulposus (NP) cells. Real-time PCR and Western blots showed that leptin increased the mRNA and protein expression of ADAMTS-4 and ADAMTS-5 and reduced the level of aggrecan in NP cells, accompanied by a prominent induction of p38 phosphorylation. Treatment of NP cells with SB203580 (a p38 inhibitor) abolished the regulation of aggrecan and ADAMTSs by leptin. Knockdown of ADAMTS-4 and ADAMTS-5 by siRNAs also attenuated the degradation of aggrecan in leptin-stimulated NP cells. To conclude, we demonstrated that leptin induces p38 to upregulate ADAMTSs and thereby promoting aggrecan degradation in human NP cells. These results provide a novel mechanistic insight into the molecular pathogenesis of obesity-associated IDD.
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影响因子：
2.4
作者：
Hsieh AH;Twomey JD
通讯作者：
Twomey JD
影响因子：
4.8
作者：
Abbaszade, I;Liu, RQ;Burn, TC
通讯作者：
Burn, TC
瘦素与心血管疾病
DOI：
10.1111/j.1440-1681.2011.05619.x
发表时间：
2011-12-01
影响因子：
2.9
作者：
Hou, Ning;Luo, Jian-Dong
通讯作者：
Luo, Jian-Dong
影响因子：
--
作者：
Demircan, K;Hirohata, S;Ninomiya, Y
通讯作者：
Ninomiya, Y
影响因子：
4.8
作者：
Akhatib, Bashar;Onnerfjord, Patrik;Haglund, Lisbet
通讯作者：
Haglund, Lisbet