Follistatin-Like 1 Promotes Bleomycin-Induced Pulmonary Fibrosis Through the Transforming Growth Factor Beta 1/Mitogen-Activated Protein Kinase Signaling Pathway

Follistatin-Like 1 Promotes Bleomycin-Induced Pulmonary Fibrosis Through the Transforming Growth Factor Beta 1/Mitogen-Activated Protein Kinase Signaling Pathway

Pulmonary fibrosis, a progressive lung disease where scar tissue replaces healthy tissue, affects over 5 million people globally—and for most, there’s no cure. Breathlessness worsens over time, and life expectancy after diagnosis is often just 3–5 years. Scientists have long hunted for the molecular “switches” that drive this scarring, and a 2018 study uncovered a critical player: follistatin-like 1 (FSTL1), a protein linked to tissue repair. Now, a correction to that research ensures the scientific community has accurate data to build on this breakthrough, keeping hope alive for patients and researchers alike.

Led by Jin YK and colleagues, the original study—published in the Chinese Medical Journal (Volume 131, Issue 16)—focused on how FSTL1 fuels fibrosis in mice exposed to bleomycin, a chemotherapy drug that induces lung scarring (a common model for human fibrosis). The team tested mouse lung fibroblast cells (MLgs)—the cells that produce the collagen that scars lungs—using three key assays:

• MTT: Measures cell proliferation (growth).
• Transwell migration: Tracks how cells move through barriers.
• Transwell invasion: Checks if cells can spread into new tissue (a hallmark of fibrosis).

The results were clear: FSTL1 significantly boosted fibroblast growth, migration, and invasion compared to control groups (treated with DMSO, a neutral solvent). But the team went further: they traced FSTL1’s effects to a well-studied signaling cascade: transforming growth factor-beta 1 (TGF-beta 1) and its downstream targets, the mitogen-activated protein kinases (MAPK). Specifically, FSTL1 activated three pathways: p38, JNK, and Smad2/3. When they used inhibitors to block these pathways—like SB202190 (for p38) or SP600125 (for JNK)—FSTL1’s harmful effects slowed dramatically. This was a game-changer: it suggested targeting these pathways could stop FSTL1 from scarring lungs.

However, the study’s original Figure 4C—showing fibroblast invasion—contained a critical error: identical images were mistakenly used for two conditions (FSTL1/DMSO and TGF-b1/U0126). For researchers, visuals are as important as numbers—mixing up images could lead to misinterpretations. In 2020, the Chinese Medical Journal published a corrigendum (Volume 133, Issue 14) to fix this. The updated Figure 4C replaces the duplicate images with accurate data, confirming the original findings: FSTL1 increases invasion by 2–3 times compared to controls, with statistically significant results (∗P < 0.001, †P < 0.01).

Why does this correction matter? For a disease with no cure, every accurate data point is a lifeline. The original study’s focus on FSTL1 was groundbreaking—FSTL1 is overexpressed in the lungs of people with fibrosis, and blocking it could reduce scarring. The corrected Figure 4 reinforces this: the data still holds, and the pathways remain valid targets for new therapies.

For patients, this means progress. Pulmonary fibrosis research is a race against time, and scientists can’t afford missteps. The corrected figure ensures labs can build on the study with confidence—whether they’re testing FSTL1 inhibitors in mice or studying FSTL1 levels in human patients. For clinicians, it’s a reminder that even small errors can have big impacts—and that transparency (like publishing corrigenda) is key to trustworthy science.

The original study’s findings still stand: FSTL1 is a driver of pulmonary fibrosis, and its effects run through TGF-beta 1 and MAPK signaling. With the corrected data, researchers are one step closer to turning this discovery into treatments—treatments that could give patients more time to breathe, more time with loved ones.

Jin YK, Li XH, Wang W, Liu J, Zhang W, Fang YS, Zhang ZF, Dai HP, Ning W, Wang C. Follistatin-Like 1 Promotes Bleomycin-Induced Pulmonary Fibrosis through the Transforming Growth Factor Beta 1/Mitogen-Activated Protein Kinase Signaling Pathway. Chin Med J 2018;131:1917–1925.

doi:10.4103/0366-6999.238151

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