LECT2 Human

What is LECT2 and what are its primary biological functions?

LECT2 is a secretory protein originally identified during screening for novel neutrophil chemotactic proteins. Although initially characterized from bovine origin in fetal calf serum, subsequent studies led to the cloning and structural characterization of the human analogue . LECT2 functions as a multifunctional protein involved in:

• Chemotaxis of immune cells

• Cell proliferation regulation

• Inflammatory modulation

• Immunoregulatory processes

• Carcinogenesis

The protein negatively regulates the homeostasis of natural killer T cells in the liver and is believed to play critical roles in tissue growth and repair following damage . To investigate these functions, researchers typically employ cellular migration assays, proliferation studies, and immunomodulatory experimental designs.

How is LECT2 gene structured and where is it primarily expressed?

The human LECT2 gene consists of four exons and three introns, mapped to chromosome 5q31.1-q32, which is a cluster harboring several genes encoding immunoregulatory cytokines . This chromosomal location suggests potential co-regulation with other immune mediators.

Table 1: Key Structural Features of Human LECT2

LECT2 is expressed preferentially by human adult and fetal liver cells and is secreted into the bloodstream . Methodological approaches for studying expression patterns include quantitative PCR, immunohistochemistry, and ELISA assays for serum quantification.

What post-translational modifications are important for LECT2 function?

Human LECT2 protein contains three internal disulfide connections (Cys25-Cys60; Cys36-Cys41; Cys99-Cys142). These disulfide bonds are crucial for maintaining the protein's structural integrity and function . Notably, zinc binds to these disulfide bonds to inhibit the protein's function, suggesting an important regulatory mechanism .

To study these post-translational modifications, researchers commonly employ:

• Mass spectrometry for characterizing disulfide patterns

• Site-directed mutagenesis of cysteine residues to evaluate functional importance

• Metal chelation assays to study zinc binding effects on activity

How is LECT2 involved in liver diseases and hepatic pathologies?

LECT2 plays significant roles in multiple liver pathologies. Research indicates its involvement in:

• Hepatocarcinogenesis (liver cancer development)

• Liver fibrosis

• Acute liver injury responses

Experimental evidence from Xie et al. demonstrated that LECT2 mRNA and serum levels increase during the early phase (first to second days) of liver injury exacerbation in models using carbon tetrachloride and concanavalin A . Their findings showed that LECT2-knockout mice exhibited less liver injury and reduced macrophage infiltration compared to wild-type counterparts .

One study revealed that LECT2 "controls inflammatory monocytes to constrain growth and progression of hepatocellular carcinoma" and suggests it could be a beneficial immunotherapy choice for HCC .

What is LECT2 amyloidosis (ALECT2) and how is it studied?

LECT2 has been identified as one of the proteins associated with human systemic amyloidosis. Leukocyte chemotactic factor 2 amyloidosis (ALECT2) most commonly affects the kidney and liver, primarily in people of Hispanic ethnicity .

Methodological approaches for studying ALECT2 include:

• Histopathological examination with Congo red staining

• Immunohistochemistry using anti-LECT2 antibodies

• Mass spectrometry-based proteomic analysis of amyloid deposits

• Genetic analysis for variants affecting LECT2 amyloidogenicity

Understanding the molecular mechanisms of LECT2 misfolding and aggregation remains a key research challenge with implications for developing therapeutic strategies.

How does LECT2 contribute to metabolic disorders and insulin resistance?

Research has uncovered that LECT2 acts as a hepatokine connecting obesity with insulin resistance in skeletal muscle . Studies revealed that LECT2 protein hinders insulin signaling by phosphorylating Jun NH2-terminal kinase (JNK) in C2C12 myocytes .

Effective methodologies for investigating LECT2's metabolic effects include:

• Measurement of circulating LECT2 in patients with metabolic disorders

• Ex vivo muscle strip experiments to assess direct effects on insulin sensitivity

• In vivo glucose tolerance and insulin sensitivity tests in models with altered LECT2 expression

• Cell culture systems examining molecular pathways affected by LECT2 exposure

What are the optimal methods for measuring LECT2 levels in human samples?

For accurate quantification of LECT2 in human samples, several techniques are recommended:

• Enzyme-linked immunosorbent assay (ELISA)

  • Commercial kits require validation for research use

  • Custom ELISAs may be necessary for specific research questions

• Mass spectrometry-based approaches

  • Multiple reaction monitoring (MRM) assays for absolute quantification

  • Label-free quantification for relative abundance

• Western blotting

  • Useful for semi-quantitative analysis

  • Requires validation of antibody specificity

When measuring LECT2 levels, researchers should consider pre-analytical variables (sample collection, processing, storage conditions), potential circadian variations, and appropriate normalization controls.

How can LECT2 expression be manipulated in experimental models?

Several approaches can effectively modulate LECT2 expression in experimental systems:

Table 2: Methods for Manipulating LECT2 Expression

The search results mention LECT2-knockout (LECT2-ko) mice showing less liver injury in experimental models, demonstrating the utility of genetic manipulation approaches .

What protein-protein interaction methods are most effective for studying LECT2?

To effectively study LECT2's interactions with other proteins, several complementary approaches are recommended:

• Co-immunoprecipitation followed by mass spectrometry to identify binding partners

• Yeast two-hybrid screening for systematic identification of interactors

• Surface plasmon resonance (SPR) or bio-layer interferometry (BLI) for quantitative binding kinetics

• Proximity ligation assays to visualize interactions in cellular contexts

• FRET/BRET approaches for real-time monitoring of interactions in living cells

When interpreting protein interaction data, researchers should consider that LECT2's function may be context-dependent, with different interaction partners in various tissues or disease states.

What are the emerging areas of LECT2 research according to bibliometric analyses?

Comprehensive bibliometric analyses reveal several emerging LECT2 research frontiers:

Table 3: LECT2 Research Trends Based on Bibliometric Analysis

Publication trends show fluctuations with a general upward trajectory. Between 2010 and 2021, the highest annual publication count was 21 papers in 2020, with a significant increase observed from 2013 to 2014 .

How is LECT2 being investigated as a potential biomarker or therapeutic target?

Several studies are exploring LECT2's potential as a biomarker and therapeutic target:

• As a biomarker:

  • For atherosclerosis: Research by Fatma Cavide Sonmez et al. proposed LECT2 as a marker for atherosclerosis, finding overexpression in atherosclerotic areas through immunohistochemical staining

  • For liver injury: LECT2 levels increase during early phases of liver damage

  • For metabolic disorders: As a hepatokine linked to insulin resistance

• As a therapeutic target:

  • In hepatocellular carcinoma: LECT2 controls inflammatory monocytes to constrain HCC growth

  • In atherosclerosis: Modulation might affect disease progression, though findings are contradictory

  • In metabolic disorders: Targeting LECT2-mediated JNK activation could improve insulin sensitivity

What are the key experimental design considerations for studying LECT2 in inflammatory conditions?

When investigating LECT2's function in inflammation, several experimental design considerations are critical:

• Model selection:

  • Acute vs. chronic inflammation models

  • Tissue-specific inflammation (e.g., liver, joints, vascular)

  • Sterile vs. pathogen-induced inflammation

• Cell type considerations:

  • Neutrophils (given LECT2's chemotactic properties)

  • Macrophages (LECT2 affects macrophage infiltration)

  • Natural killer T cells (LECT2 regulates their homeostasis)

  • Endothelial cells (LECT2 induces adhesion molecules and cytokines)

• Appropriate readouts:

  • Inflammatory cytokine profiles (TNF-α, IL-1β, IL-8, MCP-1)

  • Immune cell recruitment and activation markers

  • Tissue damage assessment

  • Resolution phase markers

The search results note contradictory findings regarding LECT2's role in atherosclerosis. Some studies suggest it promotes inflammation by increasing adhesion molecules and cytokines in human umbilical vein endothelial cells and THP-1 cells . Other research indicates it may impede atherosclerosis progression by reducing inflammatory markers and modifying lipid profiles .

What are the major unresolved questions in LECT2 research?

Several critical knowledge gaps remain in LECT2 research:

• Receptor identification: The primary receptor(s) for LECT2 and downstream signaling pathways remain incompletely characterized.

• Tissue-specific effects: LECT2 appears to have different roles in various tissues and disease states, but the mechanisms underlying these context-dependent functions are unclear.

• Contradictory findings: As noted for atherosclerosis, LECT2's role can be both pro-inflammatory and anti-inflammatory depending on the experimental context .

• Genetic variations: The impact of genetic polymorphisms on LECT2 function and disease susceptibility requires further investigation.

• Therapeutic development: Despite promising results in preclinical models, optimal strategies for leveraging LECT2 in clinical applications remain to be determined.

How can researchers address contradictory findings in LECT2 research?

The contradictory findings regarding LECT2's role in conditions like atherosclerosis highlight important methodological considerations:

• Standardization of experimental models:

  • Use consistent cell lines and primary cell isolation protocols

  • Standardize recombinant LECT2 preparation methods

  • Establish dose-response relationships

• Context-specific analysis:

  • Evaluate tissue-specific effects systematically

  • Consider temporal aspects of LECT2 action

  • Examine interactions with other inflammatory mediators

• Translation between models:

  • Validate findings across multiple experimental systems

  • Consider species differences in LECT2 biology

  • Correlate in vitro findings with in vivo and clinical observations

Addressing these methodological challenges will be essential for resolving current contradictions in LECT2 research and establishing its true biological roles.