**1. Introduction**

Cells in virtually all tissues are in contact with organized complexes of structural molecules collectively called the extracellular matrix (ECM). ECM induces a variety of signals that regulate the behavior of cells, such as differentiation, adhesion, and migration, and also fundamental physiological processes such as embryonic development and tissue regeneration and remodeling [1]. As a consequence, tissues or organs keep their normal architecture and homeostasis. Aberrations in signal transduction from the ECM cause chronic degenerative and fibrotic disorders.

Considering the adult tissue/organ remodeling following injury, an important unresolved question is how newly deposited ECM contributes to the critical turning point from normal to abnormal healing. Wound healing is a crucial response to maintain tissue/organ structure and integrity after tissue damage, and also tissue/organ homeostasis [2]. Fibrosis is a part of the wound-healing response that maintains organ structure and integrity following tissue damage. However, excessive fibrosis contributes to a number of diseases. Indeed, fibrosis is the common pathological end result of many chronic inflammatory diseases. Fibrosis is an abnormal extension of the wound-healing process that follows tissue damage, characterized by the excessive accumulation of collagenous ECMs. The hallmark of fibrosis is excessive accumulation of mainly type I collagen (Col I) containing ECMs, and therefore involves both wound-healing and fibrotic processes. Fibrosis is recognized as a major cause of morbidity and mortality in most chronic diseases and chronic graft rejection, and also influences tumor invasion and metastasis. Importantly, a critical event in all fibrotic diseases is the activation of myofibroblast, which are the key mediators of fibrotic tissue remodeling [3].

The clarification of regulatory mechanisms underlying excessive accumulation of ECMs in parenchymal organs such as livers during the development of chronic fibrotic diseases is a critical issue. However, currently, the main barrier to designing novel antifibrotic strategies is due to our insufficient understanding of the mechanisms responsible for ECM-network formations following tissue/organ injury. This gap in knowledge translates to lack of experi‐ mental models of repair *in vivo*, including gaps in the understanding of the identity and molecular control of factors and cells participating in the repair processes following injury. In this chapter, we will focus on the present knowledge of the mechanisms of the collagennetwork organization following tissue/organ damage and pathological processes of chronic fibrotic diseases.
