Renal fibrosis (RF) is an inevitable outcome of nearly all progressive chronic kidney diseases (CKD). However, effective therapies that can halt or reverse the development of RF and CKD progression remain limited. Traditional Chinese Medicine (TCM) offers a unique therapeutic approach, demonstrating significant anti-fibrotic potential through its antioxidant and anti-inflammatory pharmacological properties. However, comprehensive reviews focusing on the role of TCM in targeting signaling pathways associated with RF are still scarce. In this review, the literature was screened according to the clarity of the relevance of TCM, including the types and mechanisms of TCM. We summarize the pivotal role of the TGF-β/Smad signaling pathway in RF and provide an overview of single Chinese botanical drug, their active ingredients, and TCM compounds that ameliorate RF by modulating this pathway, aiming to establish a solid foundation for future basic and clinical research in the field of RF. While TCM holds unique advantages in treating RF, its limitations need to be addressed through scientific research and technological innovation. Future studies will focus on elucidating mechanisms, improving quality control, validating clinical efficacy, and fostering international collaboration to promote the scientific and global application of TCM in modern medicine.

Background: GPR65 is a pH-sensing G-protein-coupled receptor that acts as a key innate immune checkpoint in the human tumor microenvironment, inhibiting the release of inflammatory factors and inducing significant upregulation of tissue repair genes. However, the expression pattern and function of GPR65 in osteosarcoma (OS) remain unclear. The purpose of this study was to investigate and elucidate the role of GPR65 in the microenvironment, proliferation and migration of OS. Methods: Retrospective RNA-seq data analysis was conducted in a cohort of 97 patients with OS data in the TAEGET database. In addition, single-cell sequencing data from six surgical specimens of human OS patients was used to analyze the molecular evolution process during OS genesis. Tissues chips and bioinformatics results were used to verify GPR65 expression level in OS. MTT, colony formation, EdU assay, wound healing, transwell assay and F-actin assay were utilized to analyze cell proliferation and invasion of OS cancer cells. RNA-seq was used to explore the potential mechanism of GPR65’s role in OS. Results: GPR65 expression was significantly low in OS, and subgroup analysis found that younger OS patients, OS patients in metastatic status, and overall survival and progression free survival OS patients had lower GPR65 expression. From ScRNA-seq data of GSE162454, we found the expression of GPR65 is significantly positively correlated with CD4 + T cells CD8 + T cells and OS related macrophage infiltration. Verification experiment found that silencing the expression of GPR65 in osteosarcoma cells U2OS and HOS could promote the proliferation and invasion process, RNA-seq results showed that the role of GPR65 in OS cells was related to immune system, metabolism and signal transduction. Conclusion: The low expression of GPR65 in OS leads to high metastasis rate and poor prognosis in OS patients. The suppression of immune escape and inhibition of proliferation may be a key pathway for GPR65 to participate in the progression of OS. The current study strengthens the role of GPR65 in OS development and provides a potential biomarker for the prognosis of OS patients.