Synergy of 5-aminolevulinate supplement and CX3CR1 suppression promotes liver regeneration via elevated IGF-1 signaling.
Inadequate remnant volume and regenerative ability of the liver pose life-threatening risks to patients after partial liver transplantation (PLT) or partial hepatectomy (PHx), while few clinical treatments focus on safely accelerating regeneration. Recently, we discovered that supplementing 5-aminolevulinate (5-ALA) improves liver cold adaptation and functional recovery, leading us to uncover a correlation between 5-ALA metabolic activities and post-PLT recovery. In a mouse 2/3 PHx model, 5-ALA supplements enhanced liver regeneration, promoting infiltration and polarization of anti-inflammatory macrophages via P53 signaling. Intriguingly, chemokine receptor CX3CR1 functions to counterbalance these effects. Genetic ablation or pharmacological inhibition of CX3CR1 (AZD8797; phase II trial candidate) augmented the macrophagic production of insulin-like growth factor 1 (IGF-1) and subsequent hepatocyte growth factor (HGF) production by hepatic stellate cells. Thus, short-term treatments with both 5-ALA and AZD8797 demonstrated pro-regeneration outcomes superior to 5-ALA-only treatments in mice after PHx. Overall, our findings may inspire safe and effective strategies to better treat PLT and PHx patients.
Pubmed ID: 37578861 RIS Download
Research resources used in this publication
- Goat Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor 488 Conjugated (RRID:AB_143165) (antibody)
- Goat anti-Mouse IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 594 (RRID:AB_2534073) (antibody)
- Goat anti-Mouse IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (RRID:AB_2534069) (antibody)
- Goat anti-Rat IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 594 (RRID:AB_10561522) (antibody)
- Goat anti-Rat IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (RRID:AB_2534074) (antibody)
- Goat anti-Rabbit IgG (H+L) Secondary Antibody, HRP (RRID:AB_228341) (antibody)
- Goat anti-Mouse IgG (H+L) Secondary Antibody, HRP (RRID:AB_228307) (antibody)
- NK1.1 Monoclonal Antibody (PK136), APC-eFluor™ 780, eBioscience (RRID:AB_2735070) (antibody)
- CD3 Monoclonal Antibody (17A2), APC, eBioscience (RRID:AB_10597589) (antibody)
- APC anti-mouse F4/80 (RRID:AB_893481) (antibody)
- PE anti-mouse CD206 (MMR) (RRID:AB_10895754) (antibody)
- Brilliant Violet 510(TM) anti-mouse/human CD11b (RRID:AB_2629529) (antibody)
- PerCP/Cyanine5.5 anti-mouse CD45 (RRID:AB_893344) (antibody)
- p53 (DO-7) Mouse mAb (RRID:AB_2713958) (antibody)
- p16 (F-12) (RRID:AB_628067) (antibody)
- Mouse Anti-P21 Monoclonal antibody, Unconjugated, Clone f-5 (RRID:AB_628073) (antibody)
- Recombinant Anti-NCR1 antibody [EPR23097-35] (RRID:AB_2904203) (antibody)
- Sox9 (D8G8H) Rabbit mAb #82630 (RRID:AB_2665492) (antibody)
- Recombinant Anti-Glutamine Synthetase antibody [EPR13022(B)] (RRID:AB_2868472) (antibody)
- CCR1 Rabbit pAb (RRID:AB_2862112) (antibody)
- CD3 antibody [SP7] (RRID:AB_443425) (antibody)
- Anti-Mannose Receptor antibody (RRID:AB_1523910) (antibody)
- β-Catenin (D10A8) XP® Rabbit mAb (RRID:AB_11127855) (antibody)
- Akt (pan) (C67E7) Rabbit mAb (RRID:AB_915783) (antibody)
- Phospho-Akt (Ser473) Antibody (RRID:AB_329825) (antibody)
- IGFBP1 (H-5) (RRID:AB_629723) (antibody)
- IGF-I (W18) (RRID:AB_1124693) (antibody)
- Cyclin D1 (E3P5S) XP® Rabbit mAb (RRID:AB_2827374) (antibody)
- β-Actin (13E5) Rabbit mAb (RRID:AB_2223172) (antibody)
- F4/80 (D2S9R) XP® Rabbit mAb (RRID:AB_2799771) (antibody)
- CX3CR1 antibody (RRID:AB_306203) (antibody)
- F4/80 antibody [CI:A3-1] (RRID:AB_1140040) (antibody)
- PCNA (PC10) Mouse mAb (RRID:AB_2160343) (antibody)
- Ki67 antibody - Proliferation Marker (RRID:AB_443209) (antibody)
Additional research tools detected in this publication
None foundAntibodies used in this publication
- Goat Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor 488 Conjugated (RRID:AB_143165)
- Goat anti-Mouse IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 594 (RRID:AB_2534073)
- Goat anti-Mouse IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (RRID:AB_2534069)
- Goat anti-Rat IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 594 (RRID:AB_10561522)
- Goat anti-Rat IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (RRID:AB_2534074)
- Goat anti-Rabbit IgG (H+L) Secondary Antibody, HRP (RRID:AB_228341)
- Goat anti-Mouse IgG (H+L) Secondary Antibody, HRP (RRID:AB_228307)
- NK1.1 Monoclonal Antibody (PK136), APC-eFluor™ 780, eBioscience (RRID:AB_2735070)
- CD3 Monoclonal Antibody (17A2), APC, eBioscience (RRID:AB_10597589)
- APC anti-mouse F4/80 (RRID:AB_893481)
- PE anti-mouse CD206 (MMR) (RRID:AB_10895754)
- Brilliant Violet 510(TM) anti-mouse/human CD11b (RRID:AB_2629529)
- PerCP/Cyanine5.5 anti-mouse CD45 (RRID:AB_893344)
- p53 (DO-7) Mouse mAb (RRID:AB_2713958)
- p16 (F-12) (RRID:AB_628067)
- Recombinant Anti-NCR1 antibody [EPR23097-35] (RRID:AB_2904203)
- Mouse Anti-P21 Monoclonal antibody, Unconjugated, Clone f-5 (RRID:AB_628073)
- Sox9 (D8G8H) Rabbit mAb #82630 (RRID:AB_2665492)
- Recombinant Anti-Glutamine Synthetase antibody [EPR13022(B)] (RRID:AB_2868472)
- CCR1 Rabbit pAb (RRID:AB_2862112)
- CD3 antibody [SP7] (RRID:AB_443425)
- Anti-Mannose Receptor antibody (RRID:AB_1523910)
- β-Catenin (D10A8) XP® Rabbit mAb (RRID:AB_11127855)
- Akt (pan) (C67E7) Rabbit mAb (RRID:AB_915783)
- Phospho-Akt (Ser473) Antibody (RRID:AB_329825)
- IGFBP1 (H-5) (RRID:AB_629723)
- IGF-I (W18) (RRID:AB_1124693)
- Cyclin D1 (E3P5S) XP® Rabbit mAb (RRID:AB_2827374)
- β-Actin (13E5) Rabbit mAb (RRID:AB_2223172)
- CX3CR1 antibody (RRID:AB_306203)
- F4/80 (D2S9R) XP® Rabbit mAb (RRID:AB_2799771)
- F4/80 antibody [CI:A3-1] (RRID:AB_1140040)
- Ki67 antibody - Proliferation Marker (RRID:AB_443209)
- PCNA (PC10) Mouse mAb (RRID:AB_2160343)
Associated grants
NonePublication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This is a list of tools and resources that we have found mentioned in this publication.
Goat Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor 488 Conjugated (antibody)
RRID:AB_143165
This polyclonal targets IgG (H+L)
View all literature mentionsGoat anti-Mouse IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 594 (antibody)
RRID:AB_2534073
This polyclonal secondary targets IgG (H+L)
View all literature mentionsGoat anti-Mouse IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (antibody)
RRID:AB_2534069
This polyclonal secondary targets IgG (H+L)
View all literature mentionsGoat anti-Rat IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 594 (antibody)
RRID:AB_10561522
This polyclonal secondary targets IgG (H+L)
View all literature mentionsGoat anti-Rat IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (antibody)
RRID:AB_2534074
This polyclonal secondary targets IgG (H+L)
View all literature mentionsGoat anti-Rabbit IgG (H+L) Secondary Antibody, HRP (antibody)
RRID:AB_228341
This polyclonal secondary targets IgG (H+L)
View all literature mentionsGoat anti-Mouse IgG (H+L) Secondary Antibody, HRP (antibody)
RRID:AB_228307
This polyclonal secondary targets IgG (H+L)
View all literature mentionsNK1.1 Monoclonal Antibody (PK136), APC-eFluor™ 780, eBioscience (antibody)
RRID:AB_2735070
This monoclonal targets NK1.1
View all literature mentionsCD3 Monoclonal Antibody (17A2), APC, eBioscience (antibody)
RRID:AB_10597589
This monoclonal targets CD3
View all literature mentionsAPC anti-mouse F4/80 (antibody)
RRID:AB_893481
This monoclonal targets F4/80
View all literature mentionsPE anti-mouse CD206 (MMR) (antibody)
RRID:AB_10895754
This monoclonal targets CD206
View all literature mentionsBrilliant Violet 510(TM) anti-mouse/human CD11b (antibody)
RRID:AB_2629529
This monoclonal targets CD11b
View all literature mentionsPerCP/Cyanine5.5 anti-mouse CD45 (antibody)
RRID:AB_893344
This monoclonal targets CD45
View all literature mentionsp53 (DO-7) Mouse mAb (antibody)
RRID:AB_2713958
This monoclonal targets p53
View all literature mentionsRecombinant Anti-NCR1 antibody [EPR23097-35] (antibody)
RRID:AB_2904203
This recombinant monoclonal targets NCR1
View all literature mentionsMouse Anti-P21 Monoclonal antibody, Unconjugated, Clone f-5 (antibody)
RRID:AB_628073
This monoclonal targets CDKN1A
View all literature mentionsSox9 (D8G8H) Rabbit mAb #82630 (antibody)
RRID:AB_2665492
This monoclonal targets Sox9
View all literature mentionsRecombinant Anti-Glutamine Synthetase antibody [EPR13022(B)] (antibody)
RRID:AB_2868472
This recombinant targets Glutamine Synthetase
View all literature mentionsCD3 antibody [SP7] (antibody)
RRID:AB_443425
This monoclonal targets CD3 antibody [SP7]
View all literature mentionsAnti-Mannose Receptor antibody (antibody)
RRID:AB_1523910
This polyclonal targets Mannose Receptor
View all literature mentionsβ-Catenin (D10A8) XP® Rabbit mAb (antibody)
RRID:AB_11127855
This monoclonal targets β-Catenin
View all literature mentionsAkt (pan) (C67E7) Rabbit mAb (antibody)
RRID:AB_915783
This monoclonal targets Akt (pan) (C67E7) Rabbit mAb
View all literature mentionsPhospho-Akt (Ser473) Antibody (antibody)
RRID:AB_329825
This polyclonal targets Phospho-Akt (Ser473)
View all literature mentionsIGFBP1 (H-5) (antibody)
RRID:AB_629723
This monoclonal targets IGFBP1 (H-5)
View all literature mentionsIGF-I (W18) (antibody)
RRID:AB_1124693
This monoclonal targets Human IGF1
View all literature mentionsCyclin D1 (E3P5S) XP® Rabbit mAb (antibody)
RRID:AB_2827374
This monoclonal targets Cyclin D1
View all literature mentionsβ-Actin (13E5) Rabbit mAb (antibody)
RRID:AB_2223172
This monoclonal targets beta-Actin
View all literature mentionsCX3CR1 antibody (antibody)
RRID:AB_306203
This polyclonal targets CX3CR1
View all literature mentionsF4/80 (D2S9R) XP® Rabbit mAb (antibody)
RRID:AB_2799771
This recombinant monoclonal targets EMR1
View all literature mentionsF4/80 antibody [CI:A3-1] (antibody)
RRID:AB_1140040
This monoclonal targets F4/80 antibody [CI:A3-1]
View all literature mentionsKi67 antibody - Proliferation Marker (antibody)
RRID:AB_443209
This polyclonal targets Ki67 antibody - Proliferation Marker
View all literature mentionsPCNA (PC10) Mouse mAb (antibody)
RRID:AB_2160343
This monoclonal targets PCNA
View all literature mentionsGoat Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor 488 Conjugated (antibody)
RRID:AB_143165
This polyclonal targets IgG (H+L)
View all literature mentionsGoat anti-Mouse IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 594 (antibody)
RRID:AB_2534073
This polyclonal secondary targets IgG (H+L)
View all literature mentionsGoat anti-Mouse IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (antibody)
RRID:AB_2534069
This polyclonal secondary targets IgG (H+L)
View all literature mentionsGoat anti-Rat IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 594 (antibody)
RRID:AB_10561522
This polyclonal secondary targets IgG (H+L)
View all literature mentionsGoat anti-Rat IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (antibody)
RRID:AB_2534074
This polyclonal secondary targets IgG (H+L)
View all literature mentionsGoat anti-Rabbit IgG (H+L) Secondary Antibody, HRP (antibody)
RRID:AB_228341
This polyclonal secondary targets IgG (H+L)
View all literature mentionsGoat anti-Mouse IgG (H+L) Secondary Antibody, HRP (antibody)
RRID:AB_228307
This polyclonal secondary targets IgG (H+L)
View all literature mentionsNK1.1 Monoclonal Antibody (PK136), APC-eFluor™ 780, eBioscience (antibody)
RRID:AB_2735070
This monoclonal targets NK1.1
View all literature mentionsCD3 Monoclonal Antibody (17A2), APC, eBioscience (antibody)
RRID:AB_10597589
This monoclonal targets CD3
View all literature mentionsAPC anti-mouse F4/80 (antibody)
RRID:AB_893481
This monoclonal targets F4/80
View all literature mentionsPE anti-mouse CD206 (MMR) (antibody)
RRID:AB_10895754
This monoclonal targets CD206
View all literature mentionsBrilliant Violet 510(TM) anti-mouse/human CD11b (antibody)
RRID:AB_2629529
This monoclonal targets CD11b
View all literature mentionsPerCP/Cyanine5.5 anti-mouse CD45 (antibody)
RRID:AB_893344
This monoclonal targets CD45
View all literature mentionsp53 (DO-7) Mouse mAb (antibody)
RRID:AB_2713958
This monoclonal targets p53
View all literature mentionsMouse Anti-P21 Monoclonal antibody, Unconjugated, Clone f-5 (antibody)
RRID:AB_628073
This monoclonal targets CDKN1A
View all literature mentionsRecombinant Anti-NCR1 antibody [EPR23097-35] (antibody)
RRID:AB_2904203
This recombinant monoclonal targets NCR1
View all literature mentionsSox9 (D8G8H) Rabbit mAb #82630 (antibody)
RRID:AB_2665492
This monoclonal targets Sox9
View all literature mentionsRecombinant Anti-Glutamine Synthetase antibody [EPR13022(B)] (antibody)
RRID:AB_2868472
This recombinant targets Glutamine Synthetase
View all literature mentionsCD3 antibody [SP7] (antibody)
RRID:AB_443425
This monoclonal targets CD3 antibody [SP7]
View all literature mentionsAnti-Mannose Receptor antibody (antibody)
RRID:AB_1523910
This polyclonal targets Mannose Receptor
View all literature mentionsβ-Catenin (D10A8) XP® Rabbit mAb (antibody)
RRID:AB_11127855
This monoclonal targets β-Catenin
View all literature mentionsAkt (pan) (C67E7) Rabbit mAb (antibody)
RRID:AB_915783
This monoclonal targets Akt (pan) (C67E7) Rabbit mAb
View all literature mentionsPhospho-Akt (Ser473) Antibody (antibody)
RRID:AB_329825
This polyclonal targets Phospho-Akt (Ser473)
View all literature mentionsIGFBP1 (H-5) (antibody)
RRID:AB_629723
This monoclonal targets IGFBP1 (H-5)
View all literature mentionsIGF-I (W18) (antibody)
RRID:AB_1124693
This monoclonal targets Human IGF1
View all literature mentionsCyclin D1 (E3P5S) XP® Rabbit mAb (antibody)
RRID:AB_2827374
This monoclonal targets Cyclin D1
View all literature mentionsβ-Actin (13E5) Rabbit mAb (antibody)
RRID:AB_2223172
This monoclonal targets beta-Actin
View all literature mentionsF4/80 (D2S9R) XP® Rabbit mAb (antibody)
RRID:AB_2799771
This recombinant monoclonal targets EMR1
View all literature mentionsCX3CR1 antibody (antibody)
RRID:AB_306203
This polyclonal targets CX3CR1
View all literature mentionsF4/80 antibody [CI:A3-1] (antibody)
RRID:AB_1140040
This monoclonal targets F4/80 antibody [CI:A3-1]
View all literature mentionsPCNA (PC10) Mouse mAb (antibody)
RRID:AB_2160343
This monoclonal targets PCNA
View all literature mentionsKi67 antibody - Proliferation Marker (antibody)
RRID:AB_443209
This polyclonal targets Ki67 antibody - Proliferation Marker
View all literature mentions
