The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis
Abstract
:1. Introduction
2. The Liver as Target of Chronic Injury and Fibrosis
3. Cell Adhesion Molecules—General Aspects and their Function in Classical Cell Recruitment
4. Adhesion Molecules in Cell–ECM Interaction
5. Adhesion Molecules in Cell–Cell Interaction
6. Selectins
7. Integrins
7.1. β1-Integrins
7.2. β2-Integrins
7.3. αV-Integrins
8. Cadherins
9. Immunoglobulin Superfamily of Adhesion Molecules
9.1. ICAMs
9.2. VCAMs
9.3. PECAM-1
9.4. NCAM
9.5. JAMs
9.6. Nectins and Nectin-Like Receptors
10. Non-Classical Adhesion Molecules
10.1. VAP-1
10.2. MAdCAM-1
10.3. Stabilins
11. Adhesion Molecules as Hepatic Fibrosis Markers and as Therapeutic Targets
12. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Adhesion Molecule | Adhesion Molecule Expressing Resident and Immigrated Liver Cell Type | ECM Ligand and Counter-Receptor | Counter-receptor Expressing Resident and Immigrated Liver Cell Type |
---|---|---|---|
Selectins E-selectin P-selectin L-selectin | vEC vEC, P T | PSGL-1 PSGL-1 MECA-79, MAdCAM-1 | LC LC EC |
Integrins α1β1 (VLA-1) α2β1 (VLA-2) α3β1 (VLA-3) α4β1 (VLA-4) α5β1 (VLA-5) α6β1 (VLA-6) α11β1 αLβ2 (LFA-1) αMβ2 (Mac-1) αXβ2 (p150,95) αDβ2 αVβ1 αVβ3 αVβ5 αVβ6 αVβ8 α4β7 αEβ7 | sEC, vEC, H, HSC C, sEC, vEC, periportal H, HSC C, vEC, H sEC, LC C, sEC, vEC, H, HSC C, vEC, H HSC LC LC LC LC HSC EC, HSC EC, HSC C, H H, HSC T T, D | CL, LN CL, LN LN FN, JAM-B, MAdCAM-1, VCAM-1 FN LN CL ICAMs, JAM-A ICAM, JAM-C ICAM, JAM-C ICAM, VCAM FN, LAP-TGFβ FN, TN, VN, LAP-TGFβ, JAM-A, JAM-C VN, LAP-TGFβ FN, TN, LAP-TGFβ VN, LAP-TGFβ FN, MAdCAM-1, VCAM-1 E-cadherin | C, EC, H, HSC EC, EpC, HSC, LC EC, EpC, HSC EC, C, H, HSC EC, C, H, HSC EC, C, H, HSC EC C, H, HSC |
Adhesion Molecule | Adhesion Molecule Expressing Resident and Immigrated Liver Cell Type | Counter-Receptor | Counter-Receptor Expressing Resident and Immigrated Liver Cell Type |
---|---|---|---|
Cadherins | |||
Desmoglein Desmocollin VE-cadherin E-cadherin N-cadherin Cadherin-11 | EpC EpC EC C, periportal H, HSC H, HSC H, HSC, M | Desmoglein, Desmocollin Desmocollin, Desmoglein VE-cadherin E-cadherin, [αEβ7, KLRG1] N-cadherin Cadherin-11 | EpC EpC EC C, periportal H, HSC, [T, D, NK] H, HSC H, HSC, M |
IgCAMs | |||
ICAM-1 VCAM-1 PECAM-1 NCAM JAM-A JAM-B JAM-C | C, EC, H, HSC C, EC, HSC EC, LC C, HSC, PF EC, EpC, LC, P mouse sEC and vEC C, sEC, vEC, HSC, PF, SM human LC | ICAM-1, β2 integrins like αLβ2 VCAM-1, α4β1 PECAM-1, [αVβ3] NCAM JAM-A, αLβ2, αVβ3 JAM-C, JAM-B, [α4β1] JAM-B, JAM-C, [αMβ2, αXβ2, αVβ2] | EC, C, H, HSC, LC EC, C, HSC, LC EC, [T] C, HSC, PF EC, EpC, P, LC mouse sEC and vEC, [LC] C, sEC, vEC, HSC, PF, SM, [LC] |
Non-classical | |||
VAP-1 MAdCAM-1 Stabilin-1 | vEC, sEC, HSC vEC sEC, vEC | Siglec-9, Siglec-10 α4β1, α4β7, L-selectin αLβ2 | LC T Treg, B |
Liver Cell | Interaction Type | Functions/Effects | CAM Group Involved |
---|---|---|---|
HSC | HSC/ECM | Induction of TGFβ release Coordination of fibrogenic activation and perpetuation Perception of ECM composition Support of fibrotic ECM synthesis Coordination of motility and contractility | Integrins |
HSC/HSC | Contribution to fibrogenic activation and survival Coordination of contractility and motility | Cadherins, IgCAMs | |
HSC/sEC | Vessel wall stabilization and diameter control Support of fibrosis-associated neovascularization | IgCAMs | |
HSC/T cell | HSC activation after phagocytosis of T cells | IgCAM (ICAM-1) | |
sEC | sEC/ECM | Coordination of capillarization, proliferation and motility Support of fibrosis-associated neovascularization | Integrins |
sEC/sEC | Contribution to tissue integrity, cell polarity, functionality Coordination of motility and neovascularization | Cadherins, IgCAMs | |
sEC/HSC | sECs influence HSCs rather by soluble factors than direct cell-cell contact | IgCAMs | |
sEC/leukocyte | Leukocyte recruitment | Integrins, cadherins, IgCAMs, non-classical CAMs | |
EpC | EpC/ECM | Coordination of polarity, homeostasis, proliferation Coordination of motility | Integrins |
EpC/EpC | Contribution to tissue integrity, cell polarity, proliferation and functionality Coordination of motility | Cadherins, IgCAMs | |
EpC/leukocyte | Leukocyte recruitment, support of leukocyte survival | Integrins, cadherins, IgCAMs |
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Hintermann, E.; Christen, U. The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis. Cells 2019, 8, 1503. https://doi.org/10.3390/cells8121503
Hintermann E, Christen U. The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis. Cells. 2019; 8(12):1503. https://doi.org/10.3390/cells8121503
Chicago/Turabian StyleHintermann, Edith, and Urs Christen. 2019. "The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis" Cells 8, no. 12: 1503. https://doi.org/10.3390/cells8121503
APA StyleHintermann, E., & Christen, U. (2019). The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis. Cells, 8(12), 1503. https://doi.org/10.3390/cells8121503