How Cellular Proteins Reveal Secrets of Lichen Planus
Imagine your body's cells as a bustling city, with countless proteins as workers keeping everything functioning smoothly. Now picture what happens when this city faces a heatwave or other disaster—how would these workers cope? This is where our cellular emergency response teams, known as heat shock proteins (HSPs), spring into action.
Heat shock proteins were first discovered in fruit flies exposed to high temperatures, but they exist in all living organisms from bacteria to humans.
Recently, scientists have discovered that these molecular rescuers play a crucial role in a mysterious skin condition called lichen planus (LP), affecting millions worldwide. This inflammatory disease, which can cause itchy purple rashes on the skin and painful lesions in the mouth, has long puzzled doctors and patients alike. New research reveals that HSP60 and HSP70, two members of this protein family, are significantly overexpressed in LP tissues, offering exciting new clues about how this condition develops and potentially how we might treat it more effectively 1 .
Heat shock proteins are our cells' first responders to stress. Initially discovered in fruit flies exposed to high temperatures (hence the name), these proteins exist in all living organisms, from bacteria to humans. They function as molecular chaperones, ensuring other proteins maintain their proper shape and function, especially during cellular stress. Think of them as emergency paramedics who:
The two families we're focusing on—HSP60 and HSP70—are particularly important cellular protectors. HSP70 is expressed constitutively in most human cells and participates in antigen presentation, cell recognition, and secretion of pro-inflammatory factors like cytokines. HSP60 transports proteins across membranes by folding them properly. Both proteins release cytokines from lymphocytes and participate in the pathogenesis of autoimmune diseases and chronic inflammation 1 .
| HSP Family | Primary Functions | Cellular Location |
|---|---|---|
| HSP60 | Protein folding, mitochondrial protein import | Mitochondria |
| HSP70 | Protein folding, prevention of protein aggregation, antigen processing | Cytosol, nucleus |
| HSP90 | Regulation of signaling proteins, steroid hormone receptors | Cytosol |
| HSP27 | Actin polymerization, antioxidant defense | Cytosol |
| HSP110 | Protein folding, nucleotide exchange factor | Cytosol, nucleus |
Lichen planus is a relatively common chronic inflammatory disease that affects the skin, mucous membranes, hair, and nails. With an estimated prevalence between 0.22% and 5% worldwide, it primarily affects adults aged 30-60 and is more common among women 1 . The condition appears in various forms:
What makes OLP particularly concerning is its classification as a potentially precancerous lesion, with the development of squamous cell carcinoma being its most serious complication 1 .
of the global population affected by lichen planus
While the exact cause of lichen planus remains unknown, current evidence suggests it's a T-cell-mediated autoimmune disease where the body's immune system mistakenly attacks its own skin and mucosal cells. Various triggers may initiate this abnormal immune response, including:
These triggers potentially cause HSP overexpression following stress to oral keratinocytes, which then provides a target for T-lymphocyte reaction that results in tissue damage and lesions 1 .
A groundbreaking study conducted by researchers from Mashhad University of Medical Sciences in Iran set out to investigate whether HSP60 and HSP70 genes were expressed differently in LP tissues compared to normal healthy tissues 1 6 . Their approach was meticulous:
Paraffin-embedded tissue blocks from 112 LP lesions (56 OLP and 56 CLP samples) plus 56 biopsy samples from healthy normal participants.
OLP samples divided into two subgroups: 28 non-erosive and 28 erosive subtypes.
Using the High Pure RNA Paraffin Kit
Using Revert Aid First Strand cDNA Synthesis Kit
Quantitative Real-Time PCR with △△CT method for analysis
The results were striking:
| OLP Subtype | Epithelial Thickness | HSP70 Expression |
|---|---|---|
| Atrophic | <7 layers | Highest in basal layer |
| Classical/Normal | 7-14 layers | Moderate, full thickness |
| Acanthotic | >14 layers | Lower, mostly basal |
Understanding how scientists study heat shock proteins helps appreciate these findings. The following research reagents are essential for investigating HSP expression:
| Reagent/Technology | Primary Function | Application in HSP Research |
|---|---|---|
| High Pure RNA Paraffin Kit | RNA extraction from archived tissues | Isolate intact RNA from paraffin-embedded LP samples |
| Revert Aid First Strand cDNA Synthesis Kit | Converts RNA to cDNA | Enables gene expression analysis through PCR |
| Quantitative Real-Time PCR | Amplifies and detects specific DNA sequences | Measures HSP60 and HSP70 expression levels |
| Anti-HSP70 monoclonal antibodies | Binds specifically to HSP70 protein | Immunohistochemical detection of HSP70 in tissues |
| SYBER Green master mix | Fluorescent DNA binding dye | Detects PCR products in real-time during amplification |
A 2024 study published in the International Journal of Molecular Sciences took this investigation further by analyzing gene expression profiles of 730 inflammation-related genes across LP subtypes using NanoString technology 5 . This approach revealed unique inflammatory signatures for each LP subtype and distinct patterns of immune cell infiltration.
The findings about HSP overexpression in LP have significant implications for diagnosing and monitoring this condition. Since erosive OLP subtypes showed higher HSP expression than non-erosive subtypes, measuring HSP levels might help clinicians:
Detect patients at higher risk for more severe disease
Track disease progression and response to treatment
Detect potential precancerous changes earlier
The overexpression of both HSP60 and HSP70 in erosive OLP compared to non-erosive OLP emphasizes the possible roles of HSPs in the pathogenesis and premalignant changes of OLP lesions 1 .
Understanding HSPs' role in LP opens exciting possibilities for treatment. Potential approaches might include:
Developing drugs that specifically modulate HSP60 and HSP70 activity could help control the abnormal immune response in LP.
Since HSPs are activated by cellular stress, stress management techniques might complement medical treatments for LP.
The distinct variations in gene expression across LP subtypes suggest that tailored therapeutic approaches might be more effective 5 .
As HSP70 is involved in antigen presentation and cytokine secretion, targeting this protein might help modulate the immune response in LP 2 .
The finding that HSPs are more highly expressed in erosive OLP is particularly significant given that this form is considered potentially precancerous. HSPs not only support tumor growth and metastasis but may also help develop immune-driven treatment strategies 4 . This dual role makes them both a risk factor and a potential therapeutic target.
The discovery that heat shock proteins HSP60 and HSP70 are significantly overexpressed in lichen planus represents a remarkable convergence of cellular biology and clinical medicine. These molecular chaperones, essential for cellular survival under stress, appear to play a key role in the development and progression of this chronic inflammatory condition.
As researchers continue to unravel the complex interactions between HSPs and the immune system, we move closer to more targeted and effective treatments for lichen planus. The day may come when measuring HSP levels becomes a standard diagnostic tool, and drugs that modulate HSP activity provide relief for those suffering from this challenging condition.
What began as an observation of how fruit flies respond to heat has evolved into a sophisticated understanding of cellular stress response that illuminates the pathogenesis of disease—a powerful reminder that fundamental biological research often holds the key to solving clinical puzzles.