Fibrillar collagen types I, II, and III

Fibrillar collagens, specifically types I, II, and III, are the primary structural components of the human extracellular matrix (ECM), providing the essential tensile strength and structural integrity required for tissue function. Type I collagen is the most abundant, predominating in bone, skin, and tendons, while Type II is the principal collagenous component of articular cartilage, and Type III is found in extensible tissues such as blood vessels and the gastrointestinal tract [4, 5, 15]. These proteins are synthesized as procollagen precursors that undergo extensive post-translational modifications, including vitamin C-dependent hydroxylation, before being secreted and assembled into stable, triple-helical fibrils [13, 19]. In pathological states, the excessive and dysregulated accumulation of these collagens leads to fibrosis in organs like the liver, lungs, and heart, which can result in organ failure [1, 7]. In the tumor microenvironment, a dense collagenous stroma (desmoplasia) promotes cancer cell survival, migration, and immune evasion while acting as a physical barrier to drug delivery [7, 11]. Conversely, the degradation of Type II collagen is a primary driver of joint dysfunction in osteoarthritis [8]. Therapeutic interventions target these molecules through direct enzymatic degradation for localized fibrotic conditions, inhibition of synthesis pathways, or the use of collagen-binding domains for targeted delivery of other therapeutic agents [7, 16].

Other names

Interstitial collagenFibril-forming collagenMajor fibrillar collagens

Therapeutic strategies include the enzymatic degradation of mature collagen fibrils (e.g., collagenases), the inhibition of procollagen synthesis and secretion (e.g., TGF-beta pathway modulation), and the prevention of covalent cross-linking (e.g., LOX inhibitors) to reduce tissue stiffness and pathological accumulation.