Collagen secretion

Collagen secretion is the multi-step biological process by which procollagen molecules are synthesized, folded, and transported from the endoplasmic reticulum (ER) to the extracellular space (Saito et al., 2009, Cell). This process requires specialized molecular machinery, including the ER-resident chaperone Serpin H1 (also known as Heat Shock Protein 47 or HSP47), which stabilizes the procollagen triple helix, and the transport protein TANGO1 (MIA3), which facilitates the loading of these large cargo molecules into COPII-coated vesicles (Ishikawa et al., 2017, Current Opinion in Cell Biology; Widmer et al., 2012, Journal of Biological Chemistry). Pathological upregulation of collagen secretion is a central driver of fibrotic diseases such as idiopathic pulmonary fibrosis, liver cirrhosis, and systemic sclerosis, where excessive extracellular matrix deposition leads to organ failure (Ricard-Blum, 2011, Cold Spring Harbor Perspectives in Biology). While collagen secretion is a physiological pathway rather than a single molecular target, it serves as a critical therapeutic node in drug development. Current pharmacological interventions like pirfenidone and nintedanib indirectly modulate this pathway by inhibiting upstream signaling, while emerging therapies specifically target the secretory machinery, such as siRNA-based inhibitors of HSP47, to arrest fibrotic progression (Sato et al., 2008, Nature Biotechnology).

Other names

Procollagen traffickingCollagen exportCollagen transportCollagen exocytosis

Modulation of collagen secretion is achieved through the inhibition of collagen-specific chaperones like HSP47 to prevent proper folding, interference with COPII vesicle formation (e.g., TANGO1 inhibition), or the downregulation of upstream TGF-beta and tyrosine kinase signaling pathways that drive collagen gene expression.