Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation

Abstract

Most chronic inflammatory illnesses include fibrosis as a pathogenic characteristic. Extracellular matrix (ECM) components build up in excess to cause fibrosis or scarring. The fibrotic process finally results in organ malfunction and death if it is severely progressive. Fibrosis affects nearly all tissues of the body. The fibrosis process is associated with chronic inflammation, metabolic homeostasis, and transforming growth factor-β1 (TGF-β1) signaling, where the balance between the oxidant and antioxidant systems appears to be a key modulator in managing these processes. Virtually every organ system, including the lungs, heart, kidney, and liver, can be affected by fibrosis, which is characterized as an excessive accumulation of connective tissue components. Organ malfunction is frequently caused by fibrotic tissue remodeling, which is also frequently linked to high morbidity and mortality. Up to 45% of all fatalities in the industrialized world are caused by fibrosis, which can damage any organ. Long believed to be persistently progressing and irreversible, fibrosis has now been revealed to be a very dynamic process by preclinical models and clinical studies in a variety of organ systems. The pathways from tissue damage to inflammation, fibrosis, and/or malfunction are the main topics of this review. Furthermore, the fibrosis of different organs with their effects was discussed. Finally, we highlight many of the principal mechanisms of fibrosis. These pathways could be considered as promising targets for the development of potential therapies for a variety of important human diseases.

The Role of IL-13 and IL-4 in Adipose Tissue Fibrosis

“…In many tissues affected by fibrotic diseases, αSMA expression levels were used to identify myofibroblasts, the major collagen-producing cell type in fibrotic tissues [ 22 , 23 ]. Immunofluorescence analysis revealed that αSMA-positive cells were increased 3 to 4-fold after IL-13 or IL-4 stimulation in C3H mice ( Figure 2 D).…”

Bionic Functional Surgical Suture with Hierarchical Micro–Nano Dimensions for Rotator Cuff Repair: Inducing Process‐Matching Mechanobiological and Biological Responses Adapted to the Regeneration

“…[3,4] Notably, sustained stress sheltering by sutures at the mid-to-late healing stage might substantially hinder the positive mechanical effects on RC regeneration since the superior tissue healing and ECM remodeling processes are highly sensitive to mechanical stimulus. [25,35,60,61] Therefore, the incremental mechanobiological response of the healing tissue induced by progressive suture degradation may facilitate tissue healing and ECM remodeling for improving RC regeneration (Figure 3a).…”

“…Instead, persistent chronic inflammation and continuous vascularization would result in pathological fibrosis and tendon scarring, both harmful to RC regeneration. [35,36] A favorable environment for RC regeneration will be created by designing functional sutures specifically suited to the phased-matching biological healing requirements in this situation. [37] Therefore, in this study, we first used Poly(DL-lactide-coglycolide) (PLGA) to synthesize nanoyarns (nys), which were further braided into surgical sutures (nySS) with a triple helical and hierarchical micro-nano structure, mimicking the histological morphologies and micro-nano sizes of the RC tendon and interfascicular matrix (IFM) collagens.…”

Antioxidant therapy against TGF‐β/SMAD pathway involved in organ fibrosis

“…In the context of organ fibrosis, oxidative stress plays a critical role in the initiation and progression of the fibrotic process, 29 which is characterized by the excessive deposition of ECM proteins, and leads to the progressive loss of organ function 30 . Several studies have shown that oxidative stress can promote fibrosis by inducing the activation of fibro‐genic cells such as fibroblasts and myofibroblasts 31 …”

“…26 Moreover, ROS can inhibit the activity of matrix metalloproteinases (MMPs), which are enzymes that degrade ECM proteins, thereby impairing the process of ECM turnover and promoting fibrosis. 27,28 In the context of organ fibrosis, oxidative stress plays a critical role in the initiation and progression of the fibrotic process, 29 which is characterized by the excessive deposition of ECM proteins, and leads to the progressive loss of organ function. 30 Several studies have shown that oxidative stress can promote fibrosis by inducing the activation of fibro-genic cells such as fibroblasts and myofibroblasts.…”