ArticleInternational journal of clinical and experimental pathology2026
Distinct collagen resolution dynamics in early versus advanced liver fibrosis: a quantitative SHG/TPEF study in mice.
Article in International journal of clinical and experimental pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND &
aimsLiver fibrosis regression occurs after the source of injury is removed, but its dynamics and histologic features remain poorly characterized. Second-harmonic generation/two-photon excited fluorescence (SHG/TPEF) microscopy enables quantitative, high-resolution collagen assessment. We employed SHG/TPEF to characterize spatiotemporal collagen remodeling during spontaneous regression in carbon tetrachloride (CCl
methodsEarly- and advanced-stage liver fibrosis were established by intraperitoneal CCl
resultsSHG/TPEF imaging showed strong positive correlations with collagen proportionate area (CPA) quantified by Sirius red staining in both early- (P8: r = 0.96, P < 0.001) and advanced-stage (P12: r = 0.87, P < 0.001) fibrosis models. In early-stage fibrosis, both CPA and SHG percentage decreased significantly after 4 weeks of recovery (CPA: 1.21 ± 0.30 vs. 0.51 ± 0.15, P < 0.001; SHG: 2.13 ± 0.68 vs. 1.18 ± 0.13, P = 0.008), with no further reduction by 12 weeks (P = 0.651 and P = 0.778, respectively). In contrast, advanced-stage fibrosis showed progressive declines, with significant reductions in SHG percentage between 4 and 12 weeks (1.91 ± 0.10 vs. 1.36 ± 0.35, P = 0.023). Quantitative collagen measurements analysis revealed that 35 measurements, particularly collagen fiber number-related metrics, regressed significantly slower in P12R4 than in P8R4 mice (P < 0.05, fold change > 1.5). Notably, early-stage regression predominantly occurred within the first 4 weeks, involving total, portal, and septal collagen, whereas advanced-stage regression was delayed, occurring mainly between 4-12 weeks and affecting total, septal, and fibrillar collagen measurements.
conclusionsSHG/TPEF provides a quantitative platform for monitoring regression dynamics in preclinical settings. Advanced fibrosis resolves with a delay, underscoring stage as a critical determinant in anti-fibrotic evaluation.
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