RB1CC1-enhanced autophagy facilitates PSCs activation and pancreatic fibrogenesis in chronic pancreatitis

Cell Death & Disease
Le LiBei Sun

Abstract

Chronic pancreatitis (CP) is described as a progressive fibro-inflammatory disorder of the exocrine disease, which eventually leads to damage of the gland. Excessive activation of pancreatic stellate cells (PSCs) is a critical participant in the initiation of CP. Autophagy is involved in multiple degeneration and inflammation in acute pancreatitis and CP. In our study, we report that retinoblastoma coiled coil protein 1 (RB1CC1) expression and the autophagic level are elevated in activated PSCs. RB1CC1 is positively correlated with pancreatic fibrogenesis in tissues and plasma of CP patients. Knockdown of RB1CC1 restrains alpha smooth muscle actin (α-SMA) and collagen expressions, and autophagy in activated PSCs in vitro. Furthermore, we show that RB1CC1 induces PSC activation via binding to ULK1 promoter and the direct interaction with ULK1 protein. These suppress ULK1 expression and its kinase activity. In mice, knockdown of RB1CC1 blocks autophagy and then inhibits the pancreatic duct ligation-induced pancreatic fibrosis. Consequently, our study highlights that RB1CC1-mediated autophagy is a key event for the activation of PSCs. Inhibition of RB1CC1 alleviates autophagy, which plays a critical role in anti-fibrotic activatio...Continue Reading

References

Sep 23, 2006·Cell Death and Differentiation·M J AbedinA Kelekar
Mar 22, 2007·Molecular Cancer Research : MCR·Ugur AkarGabriel Lopez-Berestein
Apr 30, 2008·The Journal of Cell Biology·Taichi HaraNoboru Mizushima
Feb 13, 2009·Molecular Biology of the Cell·Nao HosokawaNoboru Mizushima
Feb 20, 2009·Molecular Biology of the Cell·Chang Hwa JungDo-Hyung Kim
Mar 10, 2009·Journal of Gastroenterology·Atsushi Masamune, Tooru Shimosegawa
Jan 25, 2011·Nature Cell Biology·Joungmok KimKun-Liang Guan
Mar 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Libin ShangXiaodong Wang
Jul 7, 2011·Antioxidants & Redox Signaling·Minoti ApteJeremy Wilson
Aug 31, 2012·Autophagy·Hildegard I D MackSheila M Thomas
Dec 25, 2012·Nature Structural & Molecular Biology·Noor GammohXuejun Jiang
Apr 30, 2013·Gastroenterology·Markus M Lerch, Fred S Gorelick
Apr 30, 2013·Gastroenterology·Dhiraj Yadav, Albert B Lowenfels
Nov 10, 2013·Journal of Molecular Histology·Fengfei LiZilin Sun
Jan 21, 2014·Journal of Experimental & Clinical Cancer Research : CR·Guang JiaBei Sun
Jul 18, 2015·Digestive Diseases and Sciences·Guoxiao YinMing Xiang
Mar 8, 2016·Lancet·Shounak Majumder, Suresh T Chari
May 20, 2016·Acta Neuropathologica Communications·Peter M SullivanFenghua Hu
Jul 16, 2016·Journal of Cellular and Molecular Medicine·Liang JiBei Sun
Sep 13, 2016·Scientific Reports·Wang FangSun Bei
Jan 29, 2017·Journal of Gastroenterology·Atsushi MasamuneUNKNOWN Research Committee of Intractable Pancreatic Diseases in Japan
Jul 1, 2017·Cell Death Discovery·Xiaodong ZhouFranco Fortunato
Aug 25, 2017·Cell Death & Disease·Laura E GallagherEdmond Y W Chan
Jun 29, 2018·Cancer Biology & Medicine·Chengxi LiWei Zhang

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Citations

Jul 15, 2020·Biochemical Society Transactions·Syn Kok YeoJun-Lin Guan
Jan 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Le LiBei Sun

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Methods Mentioned

BETA
density gradient centrifugation
Illumina sequencing
transfection
electrophoretic mobility shift assay
co-immunoprecipitation assay
ChIP
Co-IP

Software Mentioned

Blast2Go
Trinity
BLAST
TGICL
Primer
PROMO
Gene2promotor Tool
SOAP2
SPSS
EpiTect

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