Mechanisms of Collagen Network Organization in Response to Tissue/Organ Damage

Abstract

Fibrosis is a part of the wound-healing response to tissue damage and characterized by excessive accumulation of mainly type I collagen-containing extracellular matrices (ECMs). Transforming growth factor beta (TGF-β) is a profibrogenic master cytokine responsible for promoting differentiation of tissue-resident fibroblasts into myofibroblasts, upregulation of ECM production, and downregulation of ECM degradation. The formation of ECM is an essential response in wound healing. Fibronectin is an ECM glycoprotein substantially expressed during tissue repair. Based on in vitro findings, it has been widely accepted that collagen network organization was exclusively fibronectin matrix dependent. Unexpectedly, our fibronectin conditional knockout mouse models have demonstrated a fibronectin-independent mechanism of collagen fibril formation following injury and identified TGF-β signaling and type V collagen as essential elements for collagen fibrillogenesis. Interestingly, the targeting of the TGF-β signaling alone, as proposed in some recent antifibrotic therapies of chronic fibrotic diseases, is not sufficient to completely prevent liver fibrosis. In this chapter, we focus on the present knowledge of the mechanisms of the collagen network organization following tissue/organ damage and pathological processes of chronic fibrotic diseases.

Comparison of α-Smooth Muscle Actin (α-SMA) and Collagen Type III Expression after Conjunctival Excision Between Platelet-Rich Fibrin (PRF) Membrane and Conjunctival Autograft Treatment: An Animal Model Experimental Study on Oryctolagus cuniculus

“…Collagen type III expression significantly surpasses autograft conjunctiva in conjunctival wound healing, indicating potential fibrosis reduction with PRF. 25 Limitations of this study include a short 14-day observation period at a single time point, hindering a comprehensive assessment of PRF membrane effects on conjunctival excision healing phases. It focused on 𝛼-SMA and type III collagen, neglecting other crucial components in the healing process.…”

The dipeptide prolyl-hydroxyproline promotes cellular homeostasis and lamellipodia-driven motility via active β1-integrin in adult tendon cells

“…Pro-Hyp also affected (up to ~1.5-fold increase) the amounts of type I collagen secreted into the culture medium (data not shown). Collagen network organization is a critical process that occurs upon tissue damage and/or remodeling (57,58). We further explored the functional role of Pro-Hyp in the structural integrity of J o u r n a l P r e -p r o o f collagen in vitro.…”

“…The major ECM component in tendon tissues is type I collagen ( 31 ). We have demonstrated that there are at least two independent mechanisms underlying type I collagen fibril reorganization following adult tissue injury, a fibronectin-dependent mechanism and a transforming growth factor-beta (TGF-β)/type V collagen–dependent mechanism ( 32 , 33 ). Integrins are ECM receptors composed of transmembrane αβ heterodimeric subunits that mediate the organization of ECM, focal contacts, and actin-containing cytoskeleton ( 34 , 35 ).…”