[Effects and mechanism of age on the stiffness and the fibrotic phenotype of fibroblasts of human hypertrophic scar].
Level 5 - mechanism / opinion, no new human data
Ex vivo tissue and in vitro cell culture laboratory study.
PubMed 34689463 · doi:10.3760/cma.j.cn501120-20200810-00374
What was done
Hypertrophic scar tissues from 10 patients (young group: n=6, age 10.7±1.6 years; older group: n=4, age 40.0±2.2 years) and normal skin tissues from 10 controls (aged 7–41 years) were collected. Morphology and collagen structure were assessed by hematoxylin-eosin, Masson staining, and scanning electron microscopy. Liquid-phase atomic force microscopy measured dermal stiffness. Cultured fibroblasts were analyzed for morphology, proliferation (Ki67), fibrotic markers (α-SMA, TGF-β1, TGF-β3, type I collagen), and mechanotransduction markers (ROCK1, YAP) using immunofluorescence and RT-qPCR.
What was found
Scar collagen content was higher than in normal skin for both groups (t=8.02 and 3.15, P<0.05 or P<0.01), but collagen was denser and more abundant in young scars than in older scars (t=4.84, P<0.05). Dermal stiffness was significantly higher in older scars (50.3±1.1 kPa) than in young scars (35.2±0.8 kPa; t=11.43, P<0.05). Cultured fibroblasts showed similar morphology, α-SMA expression (t=1.14, P>0.05), and Ki67 nuclear expression across groups. However, fibroblasts from older scars had significantly higher mRNA and protein expression of TGF-β1 (mRNA t=2.87, P<0.05) and type I collagen (mRNA t=4.85, P<0.01), lower TGF-β3 mRNA (t=3.36, P<0.05), and higher expression of mechanotransduction genes ROCK1 (t=2.98, P<0.05) and YAP (t=7.60, P<0.01), along with elevated YAP protein levels.
Why it matters
This study links increased physical scar stiffness in adult versus pediatric tissue to enhanced mechanotransduction signaling via the ROCK1 and YAP pathways, providing potential mechanical targets for scar modulation.
Limits
The sample size was very small (n=10 scar cases: 6 young, 4 older), limiting statistical power and generalizability. The comparison evaluated pediatric patients (~11 years) against middle-aged adults (~40 years) rather than elderly individuals. Isolated cell culture and ex vivo tissue analyses do not fully replicate in vivo mechanical forces and dynamic wound-healing microenvironments.
Cited by
- supports Younger patients in their 20s and 30s have a higher risk of developing thicker surgical scars than patients in their 60s or 70s due to more robust collagen production.