# Wnt Signaling Pathway: Biological Function, Diseases, and Therapeutic Interventions

## TL;DR

This paper reviews the Wnt signaling pathway's role in development and disease, focusing on its contribution to tissue fibrosis and the potential of SFRPs as therapeutic targets.

## Contribution

The paper systematically examines Wnt signaling's regulatory mechanisms and therapeutic approaches, emphasizing SFRPs as promising antifibrotic targets.

## Key findings

- Wnt signaling is a central driver of fibrotic progression across multiple tissues.
- Secreted frizzled-related proteins (SFRPs) exhibit biphasic, context-dependent effects in fibrosis.
- SFRPs are highlighted as promising targets for antifibrotic intervention based on preclinical and clinical studies.

## Abstract

The Wnt signaling pathway deeply participates in multiple physiological and pathological processes. Its activity is intricately regulated by a diverse network of modulators, reflecting the pathway's structural and functional complexity. Dysregulation of Wnt signaling leads to cellular dysfunction and is associated with a wide spectrum of diseases, among which tissue fibrosis represents a major pathological outcome, characterized by activation of myofibroblasts and subsequent excessive deposition of extracellular matrix in response to injury. Wnt signaling is a central driver of fibrotic progression across multiple tissues and organs; however, effective therapeutic strategies directly targeting Wnt signaling in fibrosis remain scarce. In this review, we provide a comprehensive overview of Wnt pathway components, regulatory mechanisms, and therapeutic approaches. We systematically examine how Wnt signaling governs both developmental processes and pathological conditions, with particular emphasis on its role in fibrosis while also extending discussion to other diseases. Special attention is devoted to the secreted frizzled‐related proteins (SFRPs) family, soluble regulators with biphasic, context‐dependent effects that are especially relevant in fibrosis. Finally, we summarize insights from preclinical and clinical studies, review advances and challenges in the development of small‐molecule compounds targeting Wnt components, highlighting the vital role of SFRPs as promising targets for antifibrotic intervention.

The Wnt signaling pathway is essential for development and tissue homeostasis, while its dysregulation drives diverse diseases. This review systematically outlines its components, functions, regulators, and preclinical models, highlighting secreted frizzled‐related proteins (SFRPs) as context‐dependent, biphasic modulators. Their dual roles in tissue fibrosis underscore both the complexity of Wnt regulation and the therapeutic potential of SFRPs.