{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:03:24Z","timestamp":1787792604034,"version":"build-2784847793"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>\n                    Erectile dysfunction (ED) is a prevalent complication of both type 1 and type 2 diabetes mellitus (DM), but the shared molecular mechanisms underlying this complication remain unclear. This study employed an integrative multiomics approach to identify conserved pathways in diabetic ED. A type 2 diabetes mellitus-related erectile dysfunction (T2DM-ED) rat model was established and validated functionally. Transcriptomic analysis of cavernous tissue identified differentially expressed genes (DEGs), which were cross-referenced with a public type 1 diabetes mellitus-related erectile dysfunction (T1DM-ED) dataset, revealing 141 shared DEGs enriched in extracellular matrix (ECM)\u2013receptor interaction, focal adhesion, phosphatidylinositol 3-kinase (PI3K)\u2013protein kinase B (Akt), and advanced glycation end products (AGE)\u2013receptor for advanced glycation end products (RAGE) signaling. Machine learning prioritized five consistently downregulated hub genes (periostin [\n                    <jats:italic toggle=\"yes\">POSTN<\/jats:italic>\n                    ], elastin [\n                    <jats:italic toggle=\"yes\">ELN<\/jats:italic>\n                    ], collagen type VI alpha 3 chain [\n                    <jats:italic toggle=\"yes\">COL6A3<\/jats:italic>\n                    ], collagen type V alpha 2 chain [\n                    <jats:italic toggle=\"yes\">COL5A2<\/jats:italic>\n                    ], and secreted protein acidic and rich in cysteine [\n                    <jats:italic toggle=\"yes\">SPARC<\/jats:italic>\n                    ]), as validated by quantitative polymerase chain reaction (qPCR) and Western blot. Their encoded proteins (periostin, elastin, collagen VI, collagen V, and SPARC) were significantly suppressed. Further analysis revealed downregulation of the expression of the focal adhesion kinase (FAK)\u2013PI3K\u2013Akt survival pathway and brain-derived neurotrophic factor (BDNF) and increased apoptosis (cleaved caspase-3) and CD68\n                    <jats:sup>+<\/jats:sup>\n                    macrophage infiltration. Single-cell RNA sequencing (scRNA-seq) mapping localized these hub genes to stromal and neural cells. These findings reveal a pathological microenvironment of ECM imbalance, impaired survival signaling, and inflammation, which are common to both diabetic ED subtypes. We conclude that macrophage-driven inflammation and ECM disruption converge to inhibit FAK\u2013PI3K\u2013Akt signaling, accelerating structural and functional decline. This inflammatory\u2013ECM signaling axis represents a promising therapeutic target for diabetic ED.\n                  <\/jats:p>","DOI":"10.4103\/aja20267","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T22:33:38Z","timestamp":1782858818000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Molecular mechanisms of erectile dysfunction in type 1 and type 2 diabetic rats: a multiomics approach"],"prefix":"10.4103","author":[{"given":"Cheng","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Andrology and Sexual Medicine, The Second Hospital of Dalian Medical University, Dalian 116027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Jun","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Andrology and Sexual Medicine, The Second Hospital of Dalian Medical University, Dalian 116027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Bang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Andrology and Sexual Medicine, The Second Hospital of Dalian Medical University, Dalian 116027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Andrology and Sexual Medicine, The Second Hospital of Dalian Medical University, Dalian 116027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le-Tian","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Andrology and Sexual Medicine, The Second Hospital of Dalian Medical University, Dalian 116027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Min","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Andrology and Sexual Medicine, The Second Hospital of Dalian Medical University, Dalian 116027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Rong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Andrology and Sexual Medicine, The Second Hospital of Dalian Medical University, Dalian 116027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Andrology, Peking University First Hospital, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Andrology and Sexual Medicine, The Second Hospital of Dalian Medical University, Dalian 116027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"R1-20260630","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1186\/s12889-024-20300-7","article-title":"The 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