Related Experiment Video
Updated: Feb 12, 2026
07:51
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
1.1K
The relationship between complement C3 expression and the MUC5B genotype in pulmonary fibrosis
Tsukasa Okamoto1, Susan K Mathai1, Corinne E Hennessy1
1Department of Medicine, University of Colorado , Aurora, Colorado.
Summary
The MUC5B promoter variant, a key risk factor for idiopathic pulmonary fibrosis (IPF), is linked to increased complement component 3 (C3) expression. C3-deficient mice showed protection against lung injury, suggesting complement
Area of Science:
- Pulmonology and Immunology
- Genetic Epidemiology
- Host Defense Mechanisms
Background:
- The MUC5B promoter variant (rs35705950) is the leading genetic risk factor for idiopathic pulmonary fibrosis (IPF).
- The roles of MUC5B and the complement system in lung host defense are established, but their interplay in IPF remains unclear.
- Previous research suggests a controversial role for the complement system in IPF pathogenesis.
Purpose of the Study:
- To investigate the association between complement component 3 (C3) and MUC5B in patients with IPF.
- To evaluate the relationship between C3 and MUC5B in a mouse model of bleomycin-induced lung injury.
- To explore the potential contribution of the complement system to IPF development.
Main Methods:
- Quantified C3 gene expression in whole lung tissue from 300 IPF patients and 175 healthy controls.
- Analyzed C3 expression in relation to IPF MUC5B promoter genotypes (TT, GT, GG) and microscopic honeycombing.
- Assessed lung injury and Muc5b expression in C3-deficient and wild-type mice following bleomycin exposure.
Main Results:
- C3 expression was significantly elevated in IPF lungs compared to controls (1.40-fold increase, P < 0.0001).
- IPF patients with the highest-risk MUC5B genotype (TT) exhibited greater C3 expression compared to other genotypes (1.59-1.66-fold increase, P < 0.05).
- C3 expression was higher in IPF lungs without honeycombing than in those with honeycombing (1.40-fold increase, P < 0.01).
- Bleomycin increased Muc5b in mice, but C3-deficient mice displayed reduced bleomycin-induced lung injury.
Conclusions:
- The common MUC5B promoter variant is associated with increased C3 expression in IPF.
- The complement system, specifically C3, may play a role in the pathogenesis of IPF.
- Targeting the complement system could be a potential therapeutic strategy for IPF.
Related Concept Videos
01:27Complement System
10.9K
The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
10.9K
02:12Relationship Formation
46.3K
What do you think is the single most influential factor in determining with whom you become friends and whom you form romantic relationships? You might be surprised to learn that the answer is simple: the people with whom you have the most contact. This most important factor is proximity. You are more likely to be friends with people you have regular contact with. For example, there are decades of research that shows that you are more likely to become friends with people who live in your dorm,...
46.3K
00:49Complementation Tests
6.3K
A complementation test is a simple cross to identify whether the two mutations are located on the same gene or different genes. It was first performed by Edward Lewis in the 1940s while working on fruit flies. He developed the test to identify the location and arrangement of different mutations on chromosomes.
Organisms heterozygous for different mutations are crossed pairwise in all combinations. If present on different genes, the mutations can complement each other by providing the missing...
Organisms heterozygous for different mutations are crossed pairwise in all combinations. If present on different genes, the mutations can complement each other by providing the missing...
6.3K
01:28Ending Relationships
205
The dissolution of intimate relationships presents complex emotional and psychological challenges, particularly when emotional bonds are strong, the relationship is long-standing, and perceived alternatives are limited. This distress often intensifies in romantic breakups, where the initiator may experience greater turmoil than the rejected partner. Contributing factors include residual attachment, guilt over causing pain, and uncertainty about how to manage the situation. The stress is further...
205
01:23Cystic Fibrosis: Pathogenesis
896
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
896
01:14Pharmacokinetic–Pharmacodynamic Relationship: Duration of Dose-Effect Relationship
7
For drugs producing a quantal response, onset occurs when plasma concentration reaches a minimum effective level (Cmin). The drug's action duration depends on how long the plasma concentration remains above Cmin.Two primary factors influence this duration: dose size and the rate of drug removal from the action site. Both depend on the drug's redistribution to poorly perfused tissues and elimination processes. A larger dose promotes rapid onset and prolongs the effect's duration.Consider a...
7