CILP attenuates pulmonary fibrosis through the TGF-β1/SMAD3 pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41382307", "kind": "science-record", "revision": 4, "content_hash": "sha256:a597dd81ecdb4b9a41a3e18c2eb1f727e055d44c9390881bbe714991ad927632", "created_at": "2026-11-01T20:31:23Z", "updated_at": "2026-11-01T22:57:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "CILP attenuates pulmonary fibrosis through the TGF-β1/SMAD3 pathway.", "doi": "10.1186/s40001-025-03644-7", "pmid": "41382307", "authors": ["Hua Zou", "Jiale Dong", "Run Zhao", "Feng Liu", "Jingsong Cheng", "Xushan Li", "Chengshuo Fei", "Peng Li", "Chunlei Liu"], "journal": "European journal of medical research", "year": 2025, "abstract": "Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with poor survival, which is characterized by abnormal accumulation of fibrotic tissue in the lung parenchyma. Transforming growth factor-β1 (TGF-β) is a central profibrotic mediator, but the related mechanism of the activation of latent TGF-β has not been conclusively elucidated. A comprehensive study of mRNAs in human IPF was conducted using GSE10667 microarray data from GEO database, and the expression of cartilage intermediate layer protein (CILP) was upregulated among end-stage pulmonary fibrosis (EPF) and acute pulmonary fibrosis (APF) as compared to non-fibrosis tissues. Furthermore, CILP has protein-protein interactions with TGF-β1 through PPI analysis. Therefore, we investigated the potential effects and mechanisms of CILP in pulmonary fibrosis in pulmonary fibroblasts and BLM-induced mouse model (Eight-week-old male C57BL/6 mice, 20-22 g, purchased from the Experimental Animal Center of Guangzhou Medical University). In vitro, treatment with recombinant CILP (100 ng/mL) significantly attenuated TGF-β1-induced upregulation of collagen type I (Col1a1, p < 0.01) and α-smooth muscle actin (α-SMA, p < 0.01) in primary mouse pulmonary fibroblasts. Mechanistically, CILP suppressed TGF-β1-mediated SMAD3 phosphorylation (p-SMAD3, p < 0.001) and nuclear translocation, as confirmed by Western blotting and immunofluorescence. In the bleomycin (BLM)-induced mouse model of pulmonary fibrosis, intravenous administration of CILP (1 μg/g body weight, administered every 2 days for 4 weeks) reduced lung collagen deposition (Masson staining) by 38% (p < 0.01), lowered Ashcroft scores (from 5.8 ± 0.7 to 2.3 ± 0.4, p < 0.001), and decreased lung hydroxyproline content (a marker of collagen accumulation) by 42% (p < 0.01) compared to BLM-only controls. Clinically, serum CILP levels showed no significant difference between 17 idiopathic pulmonary fibrosis (IPF) patients and 17 non-fibrotic controls (3.2 ± 0.8 ng/mL vs. 3.5 ± 0.9 ng/mL, p > 0.05), suggesting potential lung tissue-specific action of CILP with minimal systemic off-target risk. In conclusion, CILP inhibited TGF-β1-induced fibrosis via its negative feedback loop, and may act as a promising candidate for the precaution and treatment of IPF.", "claims": [{"id": "claim-method", "statement": "Comparisons between two groups (e.g., TGF-β1 vs. TGF-β1 + CILP) were performed using unpaired Student’s t test. Comparisons among three or more groups (e.g., control, BLM 2W, BLM 4W, BLM 6W) were performed using one-way ANOVA with Tukey’s post-hoc test to correct for multiple comparisons.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41382307", "locator": "sections[11] \"Statistical analysis\" paragraph 2", "quote": "Comparisons between two groups (e.g., TGF-β1 vs. TGF-β1 + CILP) were performed using unpaired Student’s t test. Comparisons among three or more groups (e.g., control, BLM 2W, BLM 4W, BLM 6W) were performed using one-way ANOVA with Tukey’s post-hoc test to correct for multiple comparisons."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41382307", "locator": "sections[25] \"notes\" paragraph 1", "quote": "The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In the bleomycin (BLM)-induced mouse model of pulmonary fibrosis, intravenous administration of CILP (1 μg/g body weight, administered every 2 days for 4 weeks) reduced lung collagen deposition (Masson staining) by 38% (p < 0.01), lowered Ashcroft scores (from 5.8 ± 0.7 to 2.3 ± 0.4, p < 0.001), and decreased lung hydroxyproline content (a marker of collagen accumulation) by 42% (p < 0.01) compared to BLM-only controls.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41382307", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In the bleomycin (BLM)-induced mouse model of pulmonary fibrosis, intravenous administration of CILP (1 μg/g body weight, administered every 2 days for 4 weeks) reduced lung collagen deposition (Masson staining) by 38% (p < 0.01), lowered Ashcroft scores (from 5.8 ± 0.7 to 2.3 ± 0.4, p < 0.001), and decreased lung hydroxyproline content (a marker of collagen accumulation) by 42% (p < 0.01) compared to BLM-only controls."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In the bleomycin (BLM)-induced mouse model of pulmonary fibrosis, intravenous administration of CILP (1 μg/g body weight, administered every 2 days for 4 weeks) reduced lung collagen deposition (Masson staining) by 38% (p < 0.01), lowered Ashcroft scores (from 5.8 ± 0.7 to 2.3 ± 0.4, p < 0.001), and decreased lung hydroxyproline content (a marker of collagen accumulation) by 42% (p < 0.01) compared to BLM-only controls.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41382307"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Thirty-six mice were randomized into six groups (n = 6): control group, BLM (40 μ"], "order_basis": "paper_text_order:3152", "id": "assay:4"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Comparisons between two groups (e.g., TGF-β1 vs. TGF-β1 + CILP) were performed using unpaired Student’s t test. Comparisons among three or more groups (e.g., control, BLM 2W, BLM 4W, BLM 6W) were performed using one-way ANOVA with Tukey’s post-hoc test to correct for multiple comparisons."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}