Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target
Abstract
:1. Introduction
Multifunctional Role of Gelsolin in Health and Disease
2. Alterations in Plasma Gelsolin Concentrations in Different Clinical Conditions
2.1. Trauma
2.1.1. Release of Actin from Damaged Tissues as a Major Pathological Event in Trauma Patients
2.1.2. Decreased Concentrations of pGSN in Trauma Patients
2.1.3. Repletion of Physiological Level of pGSN as a Therapeutic Option in Trauma Subjects
2.2. Sepsis
2.2.1. Prognostic Value of pGSN in Sepsis Patients When Combined with Other Sepsis Biomarkers
2.2.2. Beneficial Gelsolin-Mediated Mechanisms in Animal Models of Sepsis
2.3. Infections and Infection-Associated Diseases
2.3.1. Advantageous Effect of Gelsolin on Host Anti-Infection Protection Mechanisms
2.3.2. Varied Concentrations of pGSN in Bacterial, Protozoa and Viral-Induced Diseases
2.3.3. The Clinical Potential of Application of Plasma Gelsolin as Mucolytic Agent in CF Patients
2.4. Chronic Inflammatory and Autoimmune Disorders
2.4.1. Limiting the Use of Gelsolin as a Disease Biomarker in Chronic Inflammatory Conditions
2.4.2. Uncertain Significance of Gelsolin as a Predictor in Autoimmune Diseases
2.5. Neurological and Neurodegenerative Diseases
2.5.1. Neuroprotective Role of Gelsolin in Ischemia-Induced Brain Injuries
2.5.2. The Protective Role of Gelsolin in Alzheimer’s Disease and Its Potential as an Indicator of Rapidity of Cognitive Decline
2.5.3. Pgsn-Mediated Limitation of Neuroinflammation as a Therapeutic Approach in Neurological Conditions
2.5.4. Proteolytic Cleavage of Gelsolin by Matrix Metalloproteinases in Subarachnoid Hemorrhage Patients
2.6. Cancer
2.6.1. Contradictory Effects and Expression of Gelsolin in Cancers
2.6.2. The Usefulness of pGSN in Distinguishing Cancers from Chronic Diseases and as a Predictor of Therapy Outcome
2.6.3. The Utility of Other pGSN-Containing Body Fluids in an Early Detection of Cancers
2.7. Chronic Kidney Diseases
2.7.1. The Impact of Decreased Levels of Gelsolin in Development of Kidney Diseases
2.7.2. pGSN as a Pathological Factor in IgA Nephropathy
2.8. Other Diseases
2.8.1. The Beneficial Role of Intracellular Gelsolin in Maintenance of Physiology of Pancreatic β-Cells: Anti-Diabetic Effect of Recombinant Gelsolin in an In Vivo Model of Diabetes
2.8.2. Changes of Gelsolin Concentration during Pregnancy
2.8.3. Impact of Reduced Levels of pGSN in Pre-Eclampsia Progression
2.8.4. Elevated Levels of Gelsolin in Rhabdomyolysis and Gelsolin-Related Familial Amyloidosis of Finnish Type
2.8.5. Gelsolin as a Universal Inflammatory Biomarker and Therapeutic Tool: Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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Disease | pGSN | Material | Detection Method | Suggested Mechanism of pGSN Changes | Ref. | |
---|---|---|---|---|---|---|
Trauma | Major trauma | ↓ | blood | western blot | binding of actin from damaged cells, formation of actin-gelsolin complexes | [18] |
Critically ill patients | ↓ | blood | nucleation assay | binding of actin from damaged cells, formation of actin-gelsolin complexes | [46] | |
Burns | ↓ | blood | ELISA | binding of actin from damaged cells, formation of actin-gelsolin complexes, binding of inflammatory mediators, proteolytic cleavage by MMPs (*) | [12,47,48] | |
Traumatic brain injury | ↓ | blood | ELISA | actin binding, formation of actin-gelsolin complexes, binding of inflammatory mediators and diminishing of neuroinflammation | [50] | |
CPB-ALI | ↓ | blood | ELISA | actin binding, formation of actin-gelsolin complexes, binding of inflammatory mediators | [51] | |
Acute liver injury | ↓ | blood | ELISA | binding of actin released from injured liver | [53] | |
Infections and infectious-associated diseases | Sepsis | ↓ | blood | ELISA, nucleation assay | binding of actin from damaged cells, formation of actin-gelsolin complexes, binding of inflammatory mediators | [17,54,55] |
Malaria | ↓ | blood | nucleation assay, severing assay, western blot, LC/MS/MS | binding of actin released from destroyed erythrocytes, binding of hemozoin and formation of hemozoin-gelsolin complexes | [56,57] | |
HBV-induced cirrhosis | ↓ | blood | 2-DE, MS/MS | not defined | [58] | |
HAD | ↓ | CSF | 2-DE, 2-D DIGE, western blot | not defined | [59] | |
↑ | blood | SELDI-TOF | not defined | [60] | ||
Chronic inflammatory diseases | Rheumatic arthritis | ↓ | blood, synovial fluid | nucleation assay | distribution of gelsolin into inflamed synovial joint space, binding of actin from damaged cells, formation of actin-gelsolin complexes, decreased production (*), proteolytic degradation (*), binding to plasma factors (*) | [61] |
↓ | urine | CE-MS | not defined | [62] | ||
↑ | urine | ELISA | not defined | [63] | ||
Atopic dermatitis | ↓ | blood | ELISA | binding of inflammatory mediators, prevention of Fas-induced keratinocyte apoptosis (*) | [64] | |
Neurological disorders | Alzheimer’s disease | ↓ | CSF | 2-D DIGE, MS, ELISA | not defined | [65] |
TBE, LNB | ↓ | blood | western blot | binding of actin from damaged cells, formation of actin-gelsolin complexes, binding of inflammatory mediators | [66] | |
Multiple sclerosis | ↓ | blood, CSF | western blot | binding of actin from damaged cells, binding of inflammatory mediators and diminishing of neuroinflammation | [67] | |
SAH | ↓ | blood, CSF | ELISA, western blot | proteolytical cleavage by MMP-3, MMP-1 and MMP-9 | [68,69,70] | |
Cancers | Colon cancer | ↑ | blood | ELISA, western blot | interaction with extracellular environment proteins, increase of colon cancer motility | [71] |
Pancreatic cancer and pancreatitis | ↑ | blood | SRM, ELISA | not defined | [72] | |
Breast cancer | ↓ | blood | LC-MS/MS, western blot | BRCA1-dependent recruiting of ATF-1 | [73] | |
Astrocytoma | ↓ | CSF | 2-DE, MALDI-TOF/TOFMS | cleavage by caspase activity | [74] | |
Other diseases | Chronic kidney disease | ↓ | blood | nucleation assay | impaired pGSN synthesis due to muscle wasting, actin-mediated increase of gelsolin clearance | [75] |
AAC | ↓ | blood | ELISA | not defined | [76] | |
Diabetes | ↓ | blood | LC-MS | binding of actin from damaged cells, formation of actin-gelsolin complexes, protein anabolism | [77] | |
Diabetic retinopathy | ↓ | blood | SQ-MRM, SID-MRM | not defined | [78] | |
Pre-eclampsia | ↓ | blood | ELISA | binding of actin from damaged cells, formation of actin-gelsolin complexes, proteolytic cleavage by MMPs | [79,80] | |
Rhabdomyolysis | ↑ | blood | radioimmunoassay | induced synthesis, liberation of GSN from gelsolin-actin complexes | [81] | |
FAF | ↑ | blood | nucleation assay | impaired gelsolin-actin interactions resulting from mutation in pGSN | [82] |
Disease | Used Animals | Mechanism of Therapeutic Action of Gelsolin | Ref. |
---|---|---|---|
Lung injuries | Mice, rats | decrease of acute inflammatory response, binding of inflammatory mediators, limitation of neutrophil migration, inhibition of neutrophil adhesion to endothelial surface, improvement of pulmonary microvascular functions | [38,83] |
Burns and thermal injuries | Mice | decrease of acute neuroinflammatory response, binding of inflammatory mediators, decrease of elevated caspase-3 activity, improvement of peripheral T lymphocyte functions, regulation of oxidative response, shortening of bleeding time | [42,84] |
Sepsis | Mice, rats | binding of free circulating actin released from damaged cells, decrease of acute inflammatory response, binding of inflammatory mediators | [85,86] |
Pneumonia | Mice | decrease of acute inflammatory response, binding of inflammatory mediators, improvement of bacterial clearance by macrophages via NOS3-dependent mechanism | [87] |
Alzheimer’s disease | Mice | decrease of apoptosis, regulation of oxidative response, limitation of Aβ fibrillogenesis and Aβ-induced neurotoxicity | [88,89] |
MS/EAE | Mice | decrease of acute neuroinflammatory response, binding of inflammatory mediators, regulation of oxidative response | [35] |
Diabetes | Mice | depolymerization of F-actin | [36] |
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Piktel, E.; Levental, I.; Durnaś, B.; Janmey, P.A.; Bucki, R. Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target. Int. J. Mol. Sci. 2018, 19, 2516. https://doi.org/10.3390/ijms19092516
Piktel E, Levental I, Durnaś B, Janmey PA, Bucki R. Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target. International Journal of Molecular Sciences. 2018; 19(9):2516. https://doi.org/10.3390/ijms19092516
Chicago/Turabian StylePiktel, Ewelina, Ilya Levental, Bonita Durnaś, Paul A. Janmey, and Robert Bucki. 2018. "Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target" International Journal of Molecular Sciences 19, no. 9: 2516. https://doi.org/10.3390/ijms19092516