Fibroblasts: Insights from Molecular and Pathophysiology Perspectives—2nd Edition

Dear Colleagues,

Fibroblasts are ubiquitous, spindle-shaped mesenchymal cells located in the interstitial compartments of most organs, including the skin, heart, lungs, and skeletal muscle. Once viewed mainly as “matrix-producing” cells, they are now recognized as dynamic and heterogeneous regulators of tissue architecture, mechanics, and immune signaling. Their key function is the synthesis and deposition of extracellular matrix (ECM) components—particularly collagens, fibronectin, elastin-associated proteins, and proteoglycans—supporting structural integrity and organ-specific microenvironments.

Beyond ECM production, fibroblasts actively remodel the matrix via controlled cross-linking, glycosylation, and proteolysis, driven by a balanced secretion of ECM-modifying enzymes (e.g., MMPs) and their inhibitors (TIMPs). They also act as paracrine signaling hubs, releasing cytokines, chemokines, and growth factors that coordinate inflammation and tissue repair. A central and clinically relevant feature of fibroblasts is their phenotypic plasticity: biochemical and mechanical cues (e.g., TGF-β, PDGF, and matrix stiffness) can induce transitions into activated states, including contractile myofibroblasts. Recent work highlights key mechanisms underlying these switches, such as mechanotransduction (notably YAP/TAZ), hypoxia-associated metabolic reprogramming, and shifts toward glycolysis that influence ECM synthesis and cytoskeletal remodeling. Single-cell and spatial atlases further suggest a progenitor-like “universal” fibroblast state that can diversify into activated subtypes with distinct functions—helping explain organ- and stage-specific differences in fibrosis and tumor-associated stroma.

We are pleased to announce the second edition of the Biomedicines Special Issue “Fibroblasts: Insights from Molecular and Pathophysiology Perspectives—2nd Edition”.

Following the strong interest in and broad engagement with the first edition, this volume provides an updated forum for cutting-edge research and reviews on fibroblast biology in physiology and disease. We welcome contributions addressing fibroblast heterogeneity and plasticity, ECM remodeling and mechanobiology, immunomodulatory roles, advanced experimental models (including 3D systems), and fibroblast involvement in fibrosis, chronic inflammatory diseases, organ dysfunction, and tumorigenesis. Our goal is to integrate molecular mechanisms with pathophysiological relevance to support next-generation therapeutic strategies, including approaches aimed at reversing established fibrotic remodeling and restoring tissue function.

Dr. Milena Paw
Dr. Dawid Wnuk
Guest Editors

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