NTU Developmental Biology and Regenerative Medicine

國立臺灣大學發育生物學與再生醫學研究中心

Methylglyoxal-Stimulated Mesothelial Cells Prompted Fibroblast-to-Proto-Myofibroblast Transition

Yu-Syuan Wei, Su-Yi Tsai, Shuei-Liong Lin, Yi-Ting Chen, Pei-Shiue Tsai*. Methylglyoxal-Stimulated Mesothelial Cells Prompted Fibroblasts to Proto-myofibroblasts Transition. International Journal of Molecular Sciences. 2025, 14, 2592 (SCI) 期刊全文: https://pubmed.ncbi.nlm.nih.gov/39859527/ During long-term peritoneal dialysis, peritoneal fibrosis (PF) often happens and results in ultrafiltration failure, which directly leads to the termination of dialysis. The accumulation of extracellular matrix produced from an increasing number of myofibroblasts was a hallmark characteristic of PF. To date, glucose degradation products (GDPs, i.e., methylglyoxal (MGO)) that appeared during the heating and storage of the dialysate are considered to be key components to initiating PF, but how GDPs lead to the activation of myofibroblasts in fibrotic peritoneum has not yet been fully elucidated. In this study, a mesothelial cell line (MeT-5A) and a fibroblast cell line (MRC-5) were used to investigate the transcriptomic and proteomic changes to unveil the underlying mechanism of MGO-induced PF. Our transcriptomic data from the MGO-stimulated mesothelial cells showed upregulation of genes involved in pro-inflammatory, apoptotic, and fibrotic pathways. While no phenotypic changes were noted on fibroblasts after direct MGO, supernatant from MGO-stimulated mesothelial cells promoted fibroblasts to change into proto-myofibroblasts, activated fibroblasts in the first stage toward myofibroblasts. In conclusion, this study showed that MGO-stimulated mesothelial cells promoted fibroblast-to-proto-myofibroblast transition; however, additional involvement of other factors or cells (e.g., macrophages) may be needed to complete the transformation into myofibroblasts.

Deletion of TXNDC5 downregulates TGFβ1-αSMA-mediated testicular fibrosis in mice

Ya-Yi Yang, Yi-Min Chiang, Kai-Chien Yang, Pei-Shiue Tsai*. Deletion of TXNDC5 downregulates TGFβ1-αSMA-mediated testicular fibrosis in mice. Reproduction. 2025, 169, e250022 (SCI).期刊全文: https://pubmed.ncbi.nlm.nih.gov/40261983/ Testicular torsion is a urological emergency. Delayed diagnosis and treatment hamper the testicular salvage rate and the subsequent recovery of fertility. Although detorsion surgery restores testicular blood flow, the process of torsion/detorsion leads to ischemia/reperfusion injury, which aggravates the primary damage due to the excessive generation of free radicals that disrupt antioxidant homeostasis. In the present study, we investigated the role of the endoplasmic reticulum protein, thioredoxin domain-containing protein 5, in ischemia/reperfusion-induced testicular fibrosis. We showed that, apart from disrupted testicular structure, elevated transforming growth factor beta 1, alpha-smooth muscle actin, and collagen type 1 protein expression, accompanied by TXNDC5 upregulation, were detected in mice that underwent ischemia/reperfusion injury. By Txndc5 deletion, fibrosis, redox oxidation, and extracellular matrix-associated signaling pathways and their accompanied genes/proteins were downregulated, indicating amelioration of testicular tissue damage and fibrosis in Txndc5-/- mice. With the apparent restoration of testicular structure and spermatogenesis, our study provides a potential therapeutic strategy by targeting TXNDC5 in testicular torsion patients to reduce ischemia/reperfusion-induced testicular fibrosis and to restore their fertility.

The “AID Project”: Uncovering the Mysteries of Insect vasa Genes

Chun-Che Chang, a joint faculty member of NTU CDBRM, published an insightful paper in early December 2025. Through the AID (Aphid in Drosophila) Project, his group and collaborators (including Ming-Der Lin and others) uncovered novel roles of the duplicated vasa genes in aphids, which are serious agricultural pests. By expressing aphid genes in Drosophila melanogaster—one of the best-studied model organisms—the team revealed unexpected somatic functions of these duplicated aphid vasa genes, which had long been regarded as germline-specific in most insects. Chang believes that this study will shed new light on the evolutionary and developmental roles of insect germline genes. The full article is published in the Royal Entomological Society’s journal Insect Molecular Biology:https://resjournals.onlinelibrary.wiley.com/doi/10.1111/imb.70020