Functional compensation precedes recovery of tissue mass following acute liver injury

AbstractThe liver plays a central role in metabolism, protein synthesis and detoxification. It possesses unique regenerative capacity upon injury. While many factors regulating cellular proliferation during liver repair have been identified, the mechanisms by which the injured liver maintains vital functions prior to tissue recovery are unknown. Here, we identify a new phase of functional compensation following acute liver injury that occurs prior to cellular proliferation. By coupling single-cell RNA-seq with in situ transcriptional analyses in two independent murine liver injury models, we discover adaptive reprogramming to ensure expression of both injury response and core liver function genes dependent on macrophage-derived WNT/β-catenin signaling. Interestingly, transcriptional compensation is most prominent in non-proliferating cells, clearly delineating two temporally distinct phases of liver recovery. Overall, our work describes a mechanism by which the liver maintains essential physiological functions prior to cellular reconstitution and characterizes macrophage-derived WNT signals required for this compensation.

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Functional Compensation Precedes Recovery of Tissue Mass Following Acute Liver Injury

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.03650 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1

Author(s):

Chad Walesky ◽

Kellie Kolb ◽

Carolyn Winston ◽

Jake Henderson ◽

Benjamin Kruft ◽

...

Keyword(s):

Liver Injury ◽

Acute Liver Injury ◽

Tissue Mass ◽

Functional Compensation

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Single Cell RNA‐sequencing (scRNA‐seq) Reveals Reprogramming and Functional Compensation Preceding Cellular Recovery in Multiple Models of Acute Liver Injury

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.369.4 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Chad Walesky ◽

Kellie Kolb ◽

Carolyn Winston ◽

Jake Henderson ◽

Udayan Apte ◽

...

Keyword(s):

Liver Injury ◽

Single Cell ◽

Rna Sequencing ◽

Acute Liver Injury ◽

Multiple Models ◽

Functional Compensation ◽

Single Cell Rna Sequencing

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Acetaminophen Test Battery (ATB): A Comprehensive Method to Study Acetaminophen-Induced Acute Liver Injury

Gene Expression ◽

10.3727/105221620x15901763757677 ◽

2020 ◽

Vol 20 (2) ◽

pp. 125-138 ◽

Cited By ~ 2

Author(s):

Bharat Bhushan ◽

Udayan Apte

Keyword(s):

Liver Injury ◽

Acute Liver Injury ◽

Test Battery ◽

Western World ◽

Drug Induced ◽

Technical Problems ◽

Drug Induced Liver Injury ◽

Comprehensive Method ◽

Injury Models ◽

Apap Hepatotoxicity

Acetaminophen (APAP) overdose is the major cause of acute liver failure (ALF) in the Western world. Extensive research is ongoing to identify the mechanisms of APAP-induced ALF. APAP-induced acute liver injury is also one of the most commonly studied drug-induced liver injury models in the field of hepatotoxicity. APAP toxicity is triphasic and includes three mechanistically interlinked but temporally distinct phases of initiation, progression, and recovery/regeneration. Despite how commonly it is studied, the methods to study APAP toxicity differ significantly, often leading to confusing and contradictory data. There are number of reviews on mechanisms of APAP toxicity, but a detailed mechanism-based comprehensive method and list of assays that covers all phases of APAP hepatotoxicity are missing. The goal of this review is to provide a standard protocol and guidelines to study APAP toxicity in mice including a test battery that can help investigators to comprehensively analyze APAP toxicity in the specific context of their hypothesis. Further, we will identify the major roadblocks and common technical problems that can significantly affect the results. This acetaminophen test battery (ATB) will be an excellent guide for scientists studying this most common and clinically relevant drug-induced liver injury and will also be helpful as a roadmap for hypothesis development to study novel mechanisms.

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Hepatoprotective Effects of a Chinese Herbal Formula, Longyin Decoction, on Carbon-Tetrachloride-Induced Liver Injury in Chickens

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/392743 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Chunguang Wang ◽

Tie Zhang ◽

Xuemei Cui ◽

Shuang Li ◽

Xinghua Zhao ◽

...

Keyword(s):

Liver Injury ◽

Acute Liver Injury ◽

Pectoral Muscle ◽

High Dose ◽

Herbal Formula ◽

Injury Model ◽

Hepatoprotective Effects ◽

Injury Models ◽

Qualitative Determination ◽

Different Doses

The objective of this study is to establish poultry liver injury model induced by (CCl4) and seek effective hepatoprotective herbals for clinical application. Different doses of CCl4dissolved in vegetable oil (1 : 1,V/V) were injected via pectoral muscle to induce acute liver injury model in chickens. An herbal formula, Longyin decoction, was prepared for hepatoprotection test on chicken acute liver injury models. The pathologic changes of the liver were observed, and the activities of ALT and AST were, respectively, detected to evaluate the hepatoprotective effects of Longyin decoction on chickens. The chicken acute liver injury model was successfully established by injecting CCl4via pectoral muscle. The best dose of CCl4inducing chicken liver injury was 4.0 mL/kg·BW (body weight). The results of qualitative determination by HPTLC showed that the components of Longyin decoction containedGentian, Capillaries, Gardenia,andBupleurum root. In the high-dose Longyin group and the middle-dose Longyin group, the pathological changes of the damaged liver were mitigated and the activities of ALT and AST in serum were reduced significantly. Longyin decoction has obvious hepatoprotective effect on acute liver injury induced by CCl4.

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