Contribution of collagen adhesion receptors to tissue fibrosis

Abstract

Fibrosis is the result of a wound-healing response that fails to restore normal tissue structure function. One of the critical hallmarks of fibrosis is disrupted collagen remodeling. In tissue homeostasis, the production, deposition and organization of collagen is balanced by the degradation and remodeling of collagen within the existing matrix. After injury or chronic infection, tissues initiate a wound-healing response that is intended to create a new ECM for restoring tissue structure and function. If the wound-healing response is dysregulated or if the tissue injury or infection is severe or long-lasting, collagen deposition exceeds collagen degradation and the tissue repair process leads to fibrosis. The fibrotic repair response is extraordinarily complex and involves a wide spectrum of cells, signaling pathways and regulatory systems, some of which can be readily disrupted and thereby contribute to fibrotic lesions. The dysregulated collagen remodeling is a common end-point of all fibrotic disorders, and one of the rate-limiting steps of collagen remodeling is the binding of cells to collagen fibrils by specific cell adhesion receptors. In this review, we describe how the expression and function of collagen adhesion receptors contribute to collagen processing events that contribute to tissue fibrosis. Graphical abstract Balance between collagen remodeling in health and disease.

Inflammation by activated macrophage‐like THP‐1 cells increases human dura mater cell adhesion with alteration of integrin α2β1 and matrix metalloproteinase

“…Collagen is the most abundant mammalian protein, and it plays major roles in cellular function . For example, collagen I is a major ECM component produced by fibroblasts during wound healing, and collagen IV is involved in various cellular interactions . The adhesion study showed that collagen I and IV played the most critical roles in terms of hDMC adhesion among the ECM components evaluated.…”

“…Naïve hDMCs expressed higher levels of α 1 and α 2 β 1 than α IIb β 3 and α V β 3, and co‐culture hDMCs expressed higher levels of α 2 β 1 and α IIb β 3 compared with naïve hDMCs. Integrin α 2 β 1 has a higher affinity for collagen I than for collagen IV, and integrin α 1 binds more strongly to collagen IV than to collagen I . Previous studies showed that α 2 β 1 deletion in mice reduced collagen binding and delayed platelet aggregation, triggering immediate developmental defects, but α 1 deletion simply reduced tumor vascularization without any obvious immediate developmental defect .…”

Glycated Collagen Stimulates Differentiation of Gingival Myofibroblasts

“…In this regard, observations revealed a potent effect of MGO‐treated collagen on FN protein levels and assembly. Biologic effects may derive from this change in content and organization of this glycoprotein 36 . Increased assembly of FN molecules stimulates deposition of Type I collagen fibrils, promoting development of fibrosis 21 .…”

Role of myofibroblasts in normal and pathological periodontal wound healing

“…Chronic wound healing is usually observed in susceptible subjects such as elders and diabetics among others (Posnett & Franks, ). Conversely, excessive healing can lead to the accumulation of a scar enriched in a densely cross‐linked collagenous extracellular matrix, giving rise to fibrosis (Coelho & McCulloch, ). Fibrosis is an important driver of tissue malfunction in several acute and chronic diseases affecting the heart, liver, kidney, lung, and skin (Coelho & McCulloch, ).…”

“…Conversely, excessive healing can lead to the accumulation of a scar enriched in a densely cross‐linked collagenous extracellular matrix, giving rise to fibrosis (Coelho & McCulloch, ). Fibrosis is an important driver of tissue malfunction in several acute and chronic diseases affecting the heart, liver, kidney, lung, and skin (Coelho & McCulloch, ). In global terms, fibrosis contributes to about 33% of the deaths in developed countries (Hinz, ).…”