AgingResearch.NewsJoin free
Signal Transduction and Targeted Therapy

Restoring a cell-surface protein eased lung disease in mice

In experiments involving 24 weeks of cigarette smoke exposure, mice lacking the protein had faster lung-function decline and more inflammation than their normal littermates.

Paper by Zili Zhang, Defu Li, Weiguo Kong, +24 more authorsWenju Lu
Figure 1 from Signal Transduction and Targeted Therapy
Open the figure at full size
Figure 1. Zhang et al., CC BY-NC-ND

Our read

Interventions
Studied:
Experiments in mice
Why it’s aging research:
It studies organisms or tissues that aged naturally.

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
Follow @agingbrief

C57BL/6J mice lacking Muc1, the gene for the cell-surface protein MUC1, developed worse lung disease in experiments involving 24 weeks of cigarette smoke exposure. The experiments modeled chronic obstructive pulmonary disease, which restricts airflow. Compared with mice with intact Muc1, those lacking it had faster lung-function decline, more inflammation and impaired mitochondria, the cells’ energy-producing structures.

Aged mice lacking Muc1 also developed emphysema, damage to the lung’s air sacs, without smoke exposure. Their type II alveolar cells, which line the air sacs, showed more senescence, a state in which cells stop dividing. Using a virus to restore Muc1 specifically in these cells eased smoke-induced disease. The improvement accompanied reduced inflammation, better mitochondrial function and greater ability of type II cells to become type I cells, which support gas exchange.

Why it matters

Lung-cell senescence bears on how aging may contribute to emphysema. The authors identified MUC1 as a potential target for chronic obstructive pulmonary disease, particularly emphysema.

Caveats

The gene-restoration findings came from a cigarette smoke model in mice, not from treatment trials in people with chronic obstructive pulmonary disease.

Where the evidence stands

Inflammation

Cells, worms or flies, mice and humans: replicated by independent labs.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 1,040 independent labs in 77 countries
  • 204 findings against
  • Funders: National Natural Science Foundation of China and others
  • 382 of 4,589 findings with company ties

MUC1

Cells, mice and humans: a single group. Worms or flies: nothing yet.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 4 independent labs in 3 countries
  • Funders: DKFZ and others
  • 1 of 9 findings with company ties

From the paper

Result

Specifically, rs4072037 showed P = 0.010, OR = 1.75, 95% CI = 1.15–2.68; rs12411216 showed P = 0.027, OR = 1.62, 95% CI = 1.06–2.47.

Results, Functional variants in MUC1 increase susceptibility to COPD

Limitation

First, despite achieving overall matching for age and sex in the expanded Northern cohort, residual selection bias may persist due to inherent differences between COPD patients and controls.

Discussion

Quoted word for word from the full text on nature.com.

Comments

Be the first to comment.

More on Inflammation