» Articles » PMID: 25412828

Cre-ativity in the Liver: Transgenic Approaches to Targeting Hepatic Nonparenchymal Cells

Overview
Journal Hepatology
Specialty Gastroenterology
Date 2014 Nov 22
PMID 25412828
Citations 17
Authors
Affiliations
Soon will be listed here.
Abstract

Rapid evolution in transgenic (Tg) mouse technology now permits cell-specific and temporal control of fluorescent cell-labeling and gene inactivation. Here, we discuss the principal strategies that have been utilized to target, label, and manipulate hepatic nonparenchymal cells, with emphasis on the utility of constitutive and inducible Cre-lox systems. We summarize key findings of studies employing Tg technology to target hepatic stellate cells, myofibroblasts, liver sinusoidal endothelial cells, and macrophages to illustrate the power of these approaches in identifying cell-specific molecular mechanisms critical to the pathophysiology of liver disease. Increasing adoption of Tg techniques will help to answer fundamental questions regarding the pathogenesis of hepatic diseases and provide the mechanistic rationale to allow identification of novel drug targets, ultimately translating into effective therapies for patients with liver disease.

Citing Articles

Magnoflorine ameliorates hepatic fibrosis and hepatic stellate cell activation by regulating ferroptosis signaling pathway.

Zhang M, Xu L, Zhu C, Zhang Y, Luo R, Ren J Heliyon. 2024; 10(22):e39892.

PMID: 39634391 PMC: 11615489. DOI: 10.1016/j.heliyon.2024.e39892.


Myeloid AMPK signaling restricts fibrosis but is not required for metformin improvements during CDAHFD-induced NASH in mice.

Nunes J, ODwyer C, Ghorbani P, Smith T, Chauhan S, Robert-Gostlin V J Lipid Res. 2024; 65(6):100564.

PMID: 38762124 PMC: 11222943. DOI: 10.1016/j.jlr.2024.100564.


Hepatic stellate cell-intrinsic role of SOCS1 in controlling hepatic fibrogenic response and the pro-inflammatory macrophage compartment during liver fibrosis.

Kandhi R, Yeganeh M, Yoshimura A, Menendez A, Ramanathan S, Ilangumaran S Front Immunol. 2023; 14:1259246.

PMID: 37860002 PMC: 10582746. DOI: 10.3389/fimmu.2023.1259246.


An inducible model for genetic manipulation and fate-tracing of PDGFRβ-expressing fibrogenic cells in the liver.

Hamberger F, Mederacke Y, Mederacke I Sci Rep. 2023; 13(1):7322.

PMID: 37147343 PMC: 10162963. DOI: 10.1038/s41598-023-34353-y.


Doxofylline ameliorates liver fibrosis by regulating the ferroptosis signaling pathway.

Xu L, Zhang M, Pan J, Xu X, Zhang Y, Han X Front Pharmacol. 2023; 14:1135366.

PMID: 37007035 PMC: 10063813. DOI: 10.3389/fphar.2023.1135366.


References
1.
Fan B, Malato Y, Calvisi D, Naqvi S, Razumilava N, Ribback S . Cholangiocarcinomas can originate from hepatocytes in mice. J Clin Invest. 2012; 122(8):2911-5. PMC: 3408746. DOI: 10.1172/JCI63212. View

2.
Sun Z, Miller R, Patel R, Chen J, Dhir R, Wang H . Hepatic Hdac3 promotes gluconeogenesis by repressing lipid synthesis and sequestration. Nat Med. 2012; 18(6):934-42. PMC: 3411870. DOI: 10.1038/nm.2744. View

3.
Troeger J, Mederacke I, Gwak G, Dapito D, Mu X, Hsu C . Deactivation of hepatic stellate cells during liver fibrosis resolution in mice. Gastroenterology. 2012; 143(4):1073-83.e22. PMC: 3848328. DOI: 10.1053/j.gastro.2012.06.036. View

4.
Heffner C, Pratt C, Babiuk R, Sharma Y, Rockwood S, Donahue L . Supporting conditional mouse mutagenesis with a comprehensive cre characterization resource. Nat Commun. 2012; 3:1218. PMC: 3514490. DOI: 10.1038/ncomms2186. View

5.
He J, Katschke Jr K, Gribling P, Suto E, Lee W, Diehl L . CRIg mediates early Kupffer cell responses to adenovirus. J Leukoc Biol. 2012; 93(2):301-6. DOI: 10.1189/jlb.0612311. View