Fig. 3: Nociceptive sensory neuron-derived NGF possess functional specificity to promote fibrosis.

A Schematic diagram of cholera toxin B (CTB) retrograde neuronal tracing. B Representative NeuN/CTB staining of DRG neurons (n = 6). C Relative mRNA expression of NGF, NPY, SP, and CGRP in WT mice at normal, 7, 14, and 28 days (n = 6). D Relative mRNA expression of NGF at the fibrosis site and DRG at 14 days (n = 6). E NGF protein concentration at fibrotic sites in WT and Adv^TrkA mice (pg/mg protein, n = 6). F Double IF of NGF (green) and NeuN (red) after modeling on 14 day in DRG from normal, Adv^TrkA mice injected with Veh or TMX (n = 6). Scale bars: low power image is 100 μm, and the high power image is 50 μm. G IF of NGF (green) after modeling on 14 day in fibrosis site from normal, Adv^TrkA mice injected with Veh or TMX (n = 6). Scale bars: 50 μm. H Experimental workflow of intrathecal AAV-GFP-siNGF injection. I H&E and Masson staining of WT mice with intrathecal injection of AAV-GFP-siNGF or NC at 14 days. Scale bars: 300 μm. J Adv^NGF mice experimental procedure. K CGRP (red) staining in Adv^NGF mice injected with Veh or TMX at 14 days after Modeling (n = 6). Scale bars: low power image is 100 μm, and the high power image is 50 μm. L Analysis of ROM of Adv^NGF mice (n = 6). M Double IF of αSMA (green) and Col1 (red) of Adv^NGF mice. (n = 6). Scale bars: low power image is 100 μm, and the high power image is 50 μm.Yellow dashed line shows space between tendon and surrounding tissues. Black or white dashed line shows space occupied by fibrosis tissues. T represents tendon; AD represents fibrosis tissue; M represents muscle(mean ± SD; F, G: ANOVA with multiple comparisons, I/K–M: unpaired t-test; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; A/H(mouse, injector and intrathecal space)/J created in Adobe. Author, Yanhao Li. (2025). Contact the author for publication if needed; H(tendon and fibrosis tissue) created in BioRender. Author, li, y. (2025)) https://BioRender.com/0hlz1hf).