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Cellular and Molecular Mechanisms of Chronic Inflammation-Associated Organ Fibrosis

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Chronic Inflammation

Abstract

Fibrotic or scar tissue represents a condition where normal tissue architecture has become distorted and been replaced by extracellular matrix (ECM). ECM deposition in injured tissues is a natural part of the wound healing process that facilitates efficient restoration of tissue integrity. However, if the injury persists, the excessive accumulation of ECM leads to the loss of organ function and eventual organ failure. Persistent injuries arise due to various causes, depending on the organ. Some fibrotic diseases are associated with the chronic inflammation that accompanies infection or autoimmune conditions. Other fibrotic diseases are triggered by chemical or pathophysiological insults to epithelial cells, or by unknown causes, as is the case for idiopathic pulmonary fibrosis (IPF). Although the etiology of fibrosis varies between specific diseases, the fibrotic process that takes place in each organ shares a number of common characteristics. In particular, it is widely accepted that excessive amounts of ECM components are produced by activated fibroblasts that accumulate in injured tissue. In the first half of this chapter, we discuss the controversial origin of activated fibroblasts as well as the mechanisms of their activation. In the second half of this chapter, we describe the cellular and molecular mediators that regulate fibrotic responses in the specific example of pulmonary fibrosis.

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Authors and Affiliations

  1. Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Tatsuya Tsukui, Shigeyuki Shichino, Takeshi Shimaoka, Satoshi Ueha & Kouji Matsushima

  2. AMED-CREST, Tokyo, 113-0033, Japan

    Tatsuya Tsukui, Shigeyuki Shichino, Takeshi Shimaoka, Satoshi Ueha & Kouji Matsushima

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  1. Tatsuya Tsukui
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  2. Shigeyuki Shichino
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  3. Takeshi Shimaoka
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  4. Satoshi Ueha
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Correspondence to Kouji Matsushima .

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  1. Interdisciplinary Program for Biomedical Sciences Institute for Academic Initiatives, Osaka University, Suita, Japan

    Masayuki Miyasaka

  2. Department of Immunobiology and Pharmacological Genetics Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Kiyoshi Takatsu

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Tsukui, T., Shichino, S., Shimaoka, T., Ueha, S., Matsushima, K. (2016). Cellular and Molecular Mechanisms of Chronic Inflammation-Associated Organ Fibrosis. In: Miyasaka, M., Takatsu, K. (eds) Chronic Inflammation. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56068-5_2

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