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Biglycan (BGN) is a small leucine-rich proteoglycan (SLRP) that serves as a critical structural and signaling component of the extracellular matrix (ECM) across various tissues, including skeletal muscle, bone, and connective tissue [1, 2]. It plays a pivotal role in maintaining muscle membrane integrity by recruiting and stabilizing utrophin and the dystrophin-associated protein complex (DAPC) at the sarcolemma, which is a key therapeutic strategy for Duchenne Muscular Dystrophy (DMD) to compensate for the lack of functional dystrophin [3, 4]. Beyond its structural functions, biglycan acts as a signaling molecule by interacting with growth factors like TGF-beta and functioning as a damage-associated molecular pattern (DAMP) that triggers the innate immune system through Toll-like receptors 2 and 4 (TLR2/4) [5, 6]. In pathological states, biglycan is implicated in the progression of fibrosis, chronic inflammation, and certain cancers, where its overexpression can drive tumor growth and metastasis [7, 8]. Therapeutic interventions include the development of recombinant human biglycan (e.g., TVN-102) for muscle-wasting diseases and the exploration of RNA-based therapies or antibodies to modulate its activity in inflammatory and oncological contexts [9, 10].
Utrophin recruitment and stabilization at the sarcolemma; TLR2 and TLR4 receptor modulation
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