{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:56:06Z","timestamp":1792151766694,"version":"4.4.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Myocardial fibrosis (MF) is a common pathological manifestation of end\u2010stage cardiovascular diseases such as hypertension. Hypertension increases cardiac afterload and induces fibrotic myocardial remodeling, ultimately progressing to heart failure. DDR1 (discoidin domain receptor 1), a collagen\u2010activated receptor, plays a pivotal role in multiorgan fibrosis progression. However, its specific mechanistic role in hypertension\u2010induced MF remains to be investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">A pressure overload\u2013induced MF model was established in male spontaneously hypertensive rats, and cardiac fibroblasts were stimulated with angiotensin II to induce a fibrotic phenotype. Cardiac function and fibrosis were assessed through echocardiography combined with histological\/cellular staining. Western blotting, quantitative reverse transcription polymerase chain reaction, immunoprecipitation, and ubiquitination assays were used to investigate molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Results demonstrated upregulated DDR1 expression in both activated cardiac fibroblasts and fibrotic hearts of spontaneously hypertensive rats. DDR1 inhibition improved cardiac structure and function in spontaneously hypertensive rats, while reducing the fibrotic phenotype of cardiac fibroblasts and attenuating MF progression. Mechanistically, DDR1 enhances direct interaction with SP1 (specificity protein 1), suppressing its ubiquitination and degradation. SP1 binds to the ROCK1 (rho\u2010associated protein kinase 1) gene promoter to strengthen transcriptional regulation, thereby upregulating ROCK1 and downstream profibrotic signaling pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">In summary, this study demonstrates that DDR1 is a pivotal driver of MF progression, establishing both a theoretical foundation and an experimental basis for DDR1\u2010targeted therapy in MF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.043251","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T12:43:24Z","timestamp":1772628204000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Discoidin Domain Receptor 1 Promotes Myocardial Fibrosis by Suppressing Specificity Protein 1 Ubiquitination and Degradation in Male Spontaneously Hypertensive Rats"],"prefix":"10.1161","volume":"15","author":[{"given":"Dazhou","family":"Lu","sequence":"first","affiliation":[{"name":"Qilu Hospital of Shandong University","place":["Jinan, China"]},{"name":"Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University Chest Pain Center, Qilu Hospital of Shandong University","place":["Jinan, China"]},{"name":"Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary\u2010Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University","place":["Jinan, China"]},{"name":"NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University","place":["Jinan, 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