SOX9 predicts progression toward cirrhosis in patients while its loss protects against liver fibrosis.
SOX9 predicts progression toward cirrhosis in patients while its loss protects against liver fibrosis.
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DOI：
10.15252/emmm.201707860
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发表时间：
2017-12
影响因子：
11.1
通讯作者：
Piper Hanley K
中科院分区：
文献类型：
--
作者：
Athwal VS;Pritchett J;Llewellyn J;Martin K;Camacho E;Raza SM;Phythian-Adams A;Birchall LJ;Mullan AF;Su K;Pearmain L;Dolman G;Zaitoun AM;Friedman SL;MacDonald A;Irving WL;Guha IN;Hanley NA;Piper Hanley K
纤维化和器官衰竭是许多慢性肝病的共同终点。关于引起纤维化的上游炎症机制和下游组织重塑的可能性，人们知道得很多。然而，对肝脏成纤维细胞体内调控纤维基质沉积的转录调控知之甚少。这种认识上的差距阻碍了对疾病严重程度和临床进展的分子预测，并限制了抗纤维化药物开发的靶点。在这项研究中，我们发现慢性肝病患者活检组织中SOX9的患病率与纤维化的严重程度相关，并准确地预测了疾病进展为肝硬变。在小鼠中灭活Sox9可以同时保护肝实质和胆汁纤维化，并改善肝功能和改善慢性炎症。SOX9位于机械信号转导因子YAP1的下游。这些数据证明了SOX9在肝纤维化中的作用，并为转录因子及其依赖通路作为肝纤维化患者新的诊断、预后和治疗靶点开辟了道路。
Fibrosis and organ failure is a common endpoint for many chronic liver diseases. Much is known about the upstream inflammatory mechanisms provoking fibrosis and downstream potential for tissue remodeling. However, less is known about the transcriptional regulation in vivo governing fibrotic matrix deposition by liver myofibroblasts. This gap in understanding has hampered molecular predictions of disease severity and clinical progression and restricted targets for antifibrotic drug development. In this study, we show the prevalence of SOX9 in biopsies from patients with chronic liver disease correlated with fibrosis severity and accurately predicted disease progression toward cirrhosis. Inactivation of Sox9 in mice protected against both parenchymal and biliary fibrosis, and improved liver function and ameliorated chronic inflammation. SOX9 was downstream of mechanosignaling factor, YAP1. These data demonstrate a role for SOX9 in liver fibrosis and open the way for the transcription factor and its dependent pathways as new diagnostic, prognostic, and therapeutic targets in patients with liver fibrosis.
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影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.1201840109
发表时间：
2012-06-12
影响因子：
11.1
作者：
Kisseleva, Tatiana;Cong, Min;Brenner, David A.
通讯作者：
Brenner, David A.
DOI：
10.1056/nejmra1213651
发表时间：
2013-05-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Liang TJ;Ghany MG
通讯作者：
Ghany MG
影响因子：
3.2
作者：
Lee, Ursula E.;Friedman, Scott L.
通讯作者：
Friedman, Scott L.
影响因子：
4.8
作者：
Batten, ML;Imanishi, Y;Palczewski, K
通讯作者：
Palczewski, K