Fig 2: LONP1 is down‐regulated in the kidneys of CKD patients and mice and proximal tubular‐specific overexpression of Lonp1 alleviates renal injury and mitochondrial dysfunction in UUO model AImmunohistochemical analysis of LONP1 expression in CKD children with mild (n = 11), moderate (n = 10), or severe fibrosis (n = 9). N = 4 in Normal group. Scale bar: 50 μm.BImmunohistochemical semi‐quantitative IOD analysis of LONP1.CPearson correlation analysis of LONP1 and atrophy and fibrosis score (AFS) in renal biopsy specimens.DWestern blot analysis for the expression of LONP1 in UUO models at different time points.EDensitometric analysis for the expression of LONP1 (n = 3, biological replicates).FDeposition of total fibrosis in kidney tissues was determined by Masson's trichrome staining. Scale bar: 50 μm.GSirius red staining in WT and cKI mice after UUO. Scale bar: 50 μm.HFibrotic area statistics of Sirius red staining in WT and cKI mice after UUO (n = 6 in WT+Sham group, n = 8 in cKI+Sham or WT+UUO group, n = 7 in cKI+UUO group, biological replicates).IqRT‐PCR analysis of FN1, Collagen I and Collagen III in WT and cKI mice after UUO (n = 7 in WT+Sham group, n = 8 in the other three groups, biological replicates).J, KWestern blot and densitometric analysis for the expression of FN1, Collagen I, Collagen III and TGF‐β1 (monomer) in WT and cKI mice after UUO (n = 3 or 4, biological replicates).LqRT‐PCR analysis of mtDNA expression in WT and cKI mice after UUO (n = 6 or 7, biological replicates).MSuccinate dehydrogenase (SDH) staining in WT and cKI mice after UUO. Scale bar: 50 μm.NTransmission electron microscopy images of the mitochondria in tubular cells in WT and cKI mice after UUO. Scale bar: 500 nm. Data information: In (B, E), data are presented as mean ± SEM. Student's t‐test. In (H–L), data are presented as mean ± SEM. One‐way ANOVA. Source data are available online for this figure.

Fig 3: Calvarial osteoblast progenitor haptotactic migration in mid FN1 gradient chamber. A) The forward migration index (yFMI), B) velocity, and C) Euclidean distance were compared across the groups using estimation plots to illustrate the distribution of the entire cell population. The swarmplot displays the underlying distribution, with differences compared to the blank control group plotted for all other groups as bootstrap 95% confidence intervals. Statistical analysis was performed using one‐way ANOVA test with Dunnett's multiple comparison test (p < 0.05 significance threshold). N = 150 for all groups in Figure panel (A–C). D) The number of protrusions in migrating cells was counted for the lower, mid, and upper FN1 gradient condition and compared to blank and uniform fibronectin controls. The mean is indicated with 95% confidence intervals. Statistical analysis was performed using one‐way ANOVA test with Dunnett's multiple comparison test (All groups compared to blank control). N = 28–33 cells in (D).

Fig 4: Biochemical changes and Fibronectin cleavage elicited by Adamts18.a Representative picrosirius red staining for fibrillar collagen (red) on 4th mammary gland sections from 5-week-old, pubertal WT and Adamts18−/− littermates; n = 5. Scale bar, 100 μm. b Representative western blot analysis on 3rd mammary glands of 5-week-old, pubertal WT and Adamts18−/− littermates; n = 4. β-actin loading control, MW marker in red. c Dot plots showing relative protein levels of laminin, collagen I, collagen IV, and fibronectin normalized to actin in 4 pubertal WT and Adamts18−/− littermates. Paired Student t-test, two-tailed; **p < 0.01. d, Fluorescent micrographs showing IF on 4th mammary gland sections from 5-week-old, pubertal WT and Adamts18−/− littermates for laminin, collagens I and IV as well as fibronectin (green) and DAPI nuclear stain (blue), n = 3. Arrows point to ECM density around TEBs or ducts; scale bar, 100 μm. e Representative western blot analysis on 3rd mammary glands of 14-week-old WT and Adamts18−/− littermates; n = 3. β-actin loading control, MW marker in red. f Dot plots showing relative protein levels of laminin, collagen I, collagen IV, and fibronectin normalized to actin in 3 adult WT and Adamts18−/− littermates. Paired Student t-test, two-tailed; n.s. not significant. g Dot plot showing relative transcript levels of Fn1 normalized to Hprt in 3rd mammary glands from 6 pairs of 5-week-old WT and Adamts18−/− littermates. Paired Student t-test, two-tailed, n.s. not significant. h Representative Western blot analysis of 3 independent experiments in which fibronectin (FN)−70K was incubated with purified active Adamts18 in the presence or absence of EDTA and/or protease inhibitor (PI). Anti-FN antibody specific to the N-terminal heparin-binding domain. i Western blot analysis of FN1-70K incubated with ADAMTS18 overexpressing HEK-293T cells in the presence or absence of EDTA. j Bar graph showing levels of cleaved FN in supernatants from control transfected and Adamts18 overexpressing HEK-293T cells in 2 independent experiments.

Fig 5: Changes in inflammatory response proteins in the brain induced by chest blasts. (A) Western blot images of differentially expressed proteins after chest blast exposure. The expression levels of (B) Hp, (C) Fn1, (D) Apoc3, (E) Serpina3k, and (F) Cd38 with normalized to internal control GAPDH. All experiments were repeated at least three times. All data were expressed as mean ± SEM (n = 5) and analyzed by a one-way ANOVA, followed by Tukey’s test for multiple comparisons. Differences were considered statistically significant at p < 0.05 for all analyses. ∗p < 0.05 vs. control group.