Liver regeneration biology: Implications for liver tumour therapies

Table 2 Studies of liver regeneration involving transgenic or knockout mice

Yr	First author	Gene product	Study title	Ref.
1994	Webber	TGF-α	“Overexpression of transforming growth factor-alpha causes liver enlargement and increased hepatocyte proliferation in transgenic mice”	[55]
1996	Cressman	IL-6	“Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice”	[56]
1997	Yamada	TNF	“Initiation of liver growth by tumor necrosis factor: deficient liver regeneration in mice lacking type I tumor necrosis factor receptor”	[57]
1998	Greenbaum	C/EBP-β	“CCAAT enhancer-binding protein beta is required for normal hepatocyte proliferation in mice after partial hepatectomy	[58]
1998	Rai	iNOS	“Impaired liver regeneration in inducible nitric oxide synthase-deficient mice”	[59]
1998	Roselli	uPA	“Liver regeneration is transiently impaired in urokinase-deficient mice”	[60]
1998	Yamada	TNFR-1TNFR-2	“Analysis of liver regeneration in mice lacking type 1 or type 2 tumor necrosis factor receptor: requirement for type 1 but not type 2 receptor”	[61]
2002	Anderson	PPAR-α	“Delayed liver regeneration in peroxisome proliferator-activated receptor-alpha-null mice”	[62]
2003	Leu	IGFBP-1	“Impaired hepatocyte DNA synthetic response posthepatectomy in insulin-like growth factor binding protein 1-deficient mice with defects in C/EBP beta and mitogen-activated protein kinase/extracellular signal-regulated kinase regulation”	[63]
2003	Strey	C3a/C5a	“The proinflammatory mediators C3a and C5a are essential for liver regeneration”	[64]
2004	Borowiak	Met	“Met provides essential signals for liver regeneration”	[65]
2004	Mohammed	TIMP3	“Abnormal TNF activity in Timp3(–/–) mice leads to chronic hepatic inflammation and failure of liver regeneration	[66]
2004	Nakamura	OSM	“Hepatocyte proliferation and tissue remodeling is impaired after liver injury in oncostatin M receptor knockout mice”	[67]
2004	Oe	TGF-β	“Intact signaling by transforming growth factor beta is not required for termination of liver regeneration in mice”	[68]
2005	Duffield	DTR	“Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair”	[69]
2005	Mitchell	HB-EGF	“Heparin-binding epidermal growth factor-like growth factor links hepatocyte priming with cell cycle progression during liver regeneration”	[70]
2005	Oliver	MT	“Impaired hepatic regeneration in metallothionein-I/II knockout mice”	[71]
2005	Seki	MyD88	“Contribution of Toll-like receptor/myeloid differentiation factor 88 signaling to murine liver regeneration”	[72]
2006	Fernández	Caveolin-1	“Caveolin-1 is essential for liver regeneration”	[73]
2006	Olle	MMP9	“Matrix metalloproteinase-9 is an important factor in hepatic regeneration after partial hepatectomy in mice”	[74]
2007	Mayoral	Caveolin-1	“Dispensability and dynamics of caveolin-1 during liver regeneration and in isolated hepatic Cells”	[75]
2009	Tumanov	Rag1LT	“T cell-derived lymphotoxin regulates liver regeneration”	[54]
2010	Erhardt	CCR5, CXCR3	“Tolerance induction in response to liver inflammation”	[47]
2010	Liu	GPC3	“Suppression of liver regeneration and hepatocyte proliferation in hepatocyte-targeted glypican 3 transgenic mice”	[76]
2012	Borude	FXR	“Hepatocyte-Specific Deletion of Farnesoid X Receptor Delays But Does Not Inhibit Liver Regeneration After Partial Hepatectomy in Mice”	[77]
2013	Bhave	GPC3	“Regulation of Liver Growth by Glypican 3, CD81, Hedgehog, and Hhex”	[78]
2014	Kong	FGF15	“Fibroblast growth factor 15 deficiency impairs liver regeneration in mice”	[79]
2014	Yang	Lrp5/6	“β-catenin signaling in murine liver zonation and regeneration: a Wnt-Wnt situation!”	[80]
2015	Lu	Mdm2	“Hepatic progenitor cells of biliary origin with liver repopulation capacity”	[81]
2016	Swiderska-Syn	Cre recombinase	“Hedgehog regulates yes-associated protein 1 in regenerating mouse liver”	[82]
2018	Tsagianni	MET	“Combined Systemic Disruption of MET and Epidermal Growth Factor Receptor Signaling Causes Liver Failure in Normal Mice”	[83]
2019	Asrud	Epac	“Mice depleted for Exchange Proteins Directly Activated by cAMP (Epac) exhibit irregular liver regeneration in response to partial hepatectomy”	[84]
2019	Fortier	p38α MAPK	“Hepatospecific ablation of p38α MAPK governs liver regeneration through modulation of inflammatory response to CCl 4-induced acute injury”	[85]
2019	Modares	IL-6R	“IL-6 Trans-signaling Controls Liver Regeneration After Partial Hepatectomy”	[86]
2019	Zhou	Rictor	“Mammalian Target of Rapamycin Complex 2 Signaling Is Required for Liver Regeneration in a Cholestatic Liver Injury Murine Model”	[87]
2020	Laschinger	CGRP-RAMP1	“The CGRP receptor component RAMP1 links sensory innervation with YAP activity in the regenerating liver”	[88]
2020	Seguin	Mfrn1, Mfrn2	“The mitochondrial metal transporters mitoferrin1 and mitoferrin2 are required for liver regeneration and cell proliferation in mice”	[89]
2020	Xue	GPC3	“Phosphorylated Ezrin (Thr567) Regulates Hippo Pathway and Yes-Associated Protein (Yap) in Liver”	[90]