{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:45:51Z","timestamp":1785422751379,"version":"3.56.0"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004001","name":"Guizhou Provincial Science and Technology Department","doi-asserted-by":"publisher","award":["[Grant No. ZK [2022] 338]"],"award-info":[{"award-number":["[Grant No. ZK [2022] 338]"]}],"id":[{"id":"10.13039\/501100004001","id-type":"DOI","asserted-by":"publisher"}]},{"award":["[Grant No. ZK [2022] 338]"],"award-info":[{"award-number":["[Grant No. ZK [2022] 338]"]}],"id":[{"id":"https:\/\/ror.org\/00kwnh405","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guizhou Provincial Science and Technology Platform Talent Program","award":["([Grant No. GCC [2023] 048])"],"award-info":[{"award-number":["([Grant No. GCC [2023] 048])"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetic cardiomyopathy (DCM) features progressive fibrotic remodeling, but the shared molecular circuitry connecting diabetes mellitus (DM) to cardiomyopathy (CM) remains unclear. We integrated three DM- and three CM-related Gene Expression Omnibus (GEO) datasets and corrected batch effects with sva, verified by violin plots, principal component analysis (PCA), and silhouette coefficients computed on all common genes (DM: 0.9489 to \u22120.1016; CM: 0.9693 to \u22120.045; PC1\/PC2 inter-batch differences abolished after normalization). Differential expression analysis identified 2562 DM Differentially expressed genes (DEGs) and 1414 CM DEGs, and their intersection yielded 91 common DEGs (51 upregulated, 40 downregulated). Protein\u2013protein interaction (PPI) analysis prioritized 25 hub genes, whose enrichment profiles implicated insulin resistance\/insulin signaling and adrenergic signaling in cardiomyocytes. TRRUST-based inference further defined a regulatory network centered on seven key genes (HIF-1\u03b1, ACTN4, ABCB1, LTBP1, CLU, TIMP2, and MYH11). To nominate a candidate target of oxymatrine (OMT), we performed docking and molecular dynamics (MD) simulations for representative complexes; OMT showed the most stable interaction with LTBP1, maintaining a consistently short pocket distance (~0.2 nm), the highest contact frequency, and the lowest MM\/PBSA binding free energy (\u221215.32 kcal\/mol), with favorable contributions dominated by van der Waals and nonpolar solvation terms. In primary cardiac fibroblasts (CFs), high glucose (HG, 30 mM glucose) induced proliferative and profibrotic activation, whereas OMT (0.4\u20130.8 mM) reduced HG-driven proliferation without detectable toxicity below 1.2 mM, suppressed FN, collagen I\/III, and \u03b1-SMA expression, and inhibited migration. OMT also normalized HG-induced cell-cycle skewing by restoring G0\/G1-phase occupancy and reducing S-phase entry, with effects comparable to metformin. Finally, HG increased LTBP1 expression and upregulated SMAD3\/SMAD4, while OMT attenuated LTBP1 induction and suppressed downstream TGF-\u03b2\/SMAD activation. Together, these data integrate cross-dataset transcriptomics with mechanistic validation to position LTBP1 as a putative antifibrotic node targeted by OMT, supporting inhibition of the LTBP1\/TGF-\u03b2\/SMAD axis as a candidate strategy to counter DCM-associated fibrosis.<\/jats:p>","DOI":"10.3390\/ijms27083481","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:12:26Z","timestamp":1776085946000},"page":"3481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Screening and Validation of LTBP1 as a Key Target of Oxymatrine in Inhibiting Cardiac Fibroblast Differentiation Under High Glucose Conditions: In Vitro and Bioinformatic Studies"],"prefix":"10.3390","volume":"27","author":[{"given":"Lianqing","family":"Tian","sequence":"first","affiliation":[{"name":"The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"},{"name":"The Department of Pharmacology of Materia Medica (The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province and The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Drug Ability), School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"},{"name":"The Key Laboratory of Optimal Utilization of Natural Medicine Resources (The Union Key Laboratory of Guiyang City, Guizhou Medical University), School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiquan","family":"Gan","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"},{"name":"The Department of Pharmacology of Materia Medica (The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province and The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Drug Ability), School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"},{"name":"The Key Laboratory of Optimal Utilization of Natural Medicine Resources (The Union Key Laboratory of Guiyang City, Guizhou Medical University), School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youqi","family":"Du","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"},{"name":"The Department of Pharmacology of Materia Medica (The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province and The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Drug Ability), School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"},{"name":"The Key Laboratory of Optimal Utilization of Natural Medicine Resources (The Union Key Laboratory of Guiyang City, Guizhou Medical University), School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaowen","family":"Long","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"},{"name":"The Department of Pharmacology of Materia Medica (The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province and The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Drug Ability), School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"},{"name":"The Key Laboratory of Optimal Utilization of Natural Medicine Resources (The Union Key Laboratory of Guiyang City, Guizhou Medical University), School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Churui","family":"Chang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"},{"name":"The Department of Pharmacology of Materia Medica (The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province and The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Drug Ability), School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"},{"name":"The Key Laboratory of Optimal Utilization of Natural Medicine Resources (The Union Key Laboratory of Guiyang City, Guizhou Medical University), School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangchun","family":"Shen","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, 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