کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10799007 | 1054218 | 2015 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
MKL1 is an epigenetic modulator of TGF-β induced fibrogenesis
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کلمات کلیدی
BDLMKL1TGF-βportal fibroblastEpigenetics - اپی ژنتیکchromatin immunoprecipitation - ایمن سازی کروماتینtransforming growth factor - تبدیل فاکتور رشدTranscriptional regulation - تنظیم ترانزیتیTranscription factor - عامل رونویسیLiver fibrosis - فیبروز کبدیHistone methylation - هیستون متیلاسیونbile duct ligation - پیوند مجرای صفراویCHiP - چیپCOMPASS - کمپس
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: MKL1 is an epigenetic modulator of TGF-β induced fibrogenesis MKL1 is an epigenetic modulator of TGF-β induced fibrogenesis](/preview/png/10799007.png)
چکیده انگلیسی
Transforming growth factor (TGF-β) induced activation of portal fibroblast cells serves as a primary cause for liver fibrosis following cholestatic injury. The underlying epigenetic mechanism is not clear. We studied the role of a transcriptional modulator, megakaryoblastic leukemia 1 (MKL1) in this process. We report here that MKL1 deficiency ameliorated BDL-induced liver fibrosis in mice as assessed by histological stainings and expression levels of pro-fibrogenic genes. MKL1 silencing by small interfering RNA (siRNA) abrogated TGF-β induced transactivation of pro-fibrogenic genes in portal fibroblast cells. TGF-β stimulated the binding of MKL1 on the promoters of pro-fibrogenic genes and promoted the interaction between MKL1 and SMAD3. While SMAD3 was necessary for MKL1 occupancy on the gene promoters, MKL1 depletion impaired SMAD3 binding reciprocally. TGF-β treatment induced the accumulation of trimethylated histone H3K4 on the gene promoters by recruiting a methyltransferase complex. Knockdown of individual members of this complex significantly weakened the binding of SMAD3 and down-regulated the activation of portal fibroblast cells. In conclusion, we have identified an epigenetic pathway that dictates TGF-β induced pro-fibrogenic transcription in portal fibroblast thereby providing novel insights for the development of therapeutic solutions to treat liver fibrosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms - Volume 1849, Issue 9, September 2015, Pages 1219-1228
Journal: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms - Volume 1849, Issue 9, September 2015, Pages 1219-1228
نویسندگان
Zhiwen Fan, Chenzhi Hao, Min Li, Xin Dai, Hao Qin, Jianfei Li, Huihui Xu, Xiaoyan Wu, Liping Zhang, Mingming Fang, Bisheng Zhou, Wenfang Tian, Yong Xu,