ArticleiScience2026
Hyperlipidemia exacerbates frozen shoulder fibrosis by activating the TGF-β/Smad2/3 signaling pathway via the TBX5-TNC-Itgα2 axis.
Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 authors.
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Abstract
Hyperlipidemia is strongly implicated in frozen shoulder, but the molecular mechanisms linking this systemic metabolic disorder to localized joint fibrosis remain unknown. To elucidate this, we established a hyperlipidemic rat model and employed transcriptomics, along with comprehensive molecular validation assays, in human synovial fibroblasts. We discovered that oxidized low-density lipoprotein initiates the fibrotic cascade by upregulating the transcription factor TBX5. TBX5 then transcriptionally promotes the expression of the extracellular matrix protein tenascin-C (TNC). TNC subsequently binds to integrinα2 (Itgα2) on fibroblasts, thus activating the potent profibrotic TGF-β/Smad2/3 signaling pathway.
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