The overproduction of reactive oxygen species (ROS) is linked to inflammatory bowel disease (IBD) and causes oxidative damage to DNA, proteins, and lipids. These ROS promote the initiation and progression of ulcerative colitis (UC). This study proposes a unique concept of nanomaterials with intrinsic enzyme-like activity (nanozymes) to mediate catalytic nanotherapy for IBD.

Fibrosis is a pathological feature of a variety of chronic inflammatory diseases that can affect almost all organs, which can cause severe consequences and even lead to death. Fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) due to disruption of the balance between ECM production and degradation. Although overabundance of ECM proteins has long been the focus of studies on fibrosis, another facet of the problem—impaired degradation of the ECM—is gaining increasing attention. Matrix metalloproteinase (MMP) and the tissue inhibitor of metalloproteinase (TIMP) system is the main molecular system contributing to ECM degradation, and macrophages are the major regulators of ECM. However, the relationship among macrophages, the MMP/TIMP system and the ECM is not fully understood in the context of fibrosis. Here, we discuss in detail the role played by the ECM in the development of fibrosis and highlight the macrophage-MMP-ECM interaction that is involved in fibrogenesis and may be a potential therapeutic target for fibrosis.

Intestinal fibrosis, a severe complication of Crohn’s disease (CD), is characterized by excessive extracellular matrix (ECM) deposition and induces intestinal strictures, but there are no effective antifibrosis drugs available for clinical application. We performed single-cell RNA sequencing (scRNA-Seq) of fibrotic and nonfibrotic ileal tissues from patients with CD with intestinal obstruction. Analysis revealed mesenchymal stromal cells (MSCs) as the major producers of ECM and the increased infiltration of its subset FAP ⁺ fibroblasts in fibrotic sites, which was confirmed by immunofluorescence and flow cytometry. Single-cell transcriptomic profiling of chronic dextran sulfate sodium salt murine colitis model revealed that CD81 ⁺ Pi16 ^– fibroblasts exhibited transcriptomic and functional similarities to human FAP ⁺ fibroblasts. Consistently, FAP ⁺ fibroblasts were identified as the key subtype with the highest level of ECM production in fibrotic intestines. Furthermore, specific knockout or pharmacological inhibition of TWIST1, which was highly expressed by FAP ⁺ fibroblasts, could significantly ameliorate fibrosis in mice. In addition, TWIST1 expression was induced by CXCL9 ⁺ macrophages enriched in fibrotic tissues via IL-1β and TGF-β signal. These findings suggest the inhibition of TWIST1 as a promising strategy for CD fibrosis treatment.