Tenascin-C (TNC), a non-structural extracellular matrix glycoprotein, is produced transiently during development or after injury and plays a key role in the damage and healing processes. TNC’s possible significance in the pathophysiology of IgA nephropathy (IgAN) is unknown.
TNC immunohistochemistry labeling was performed on paraffin-embedded slices from 107 IgAN patients’ renal biopsies, and a correlation analysis was performed between mesangial TNC expression and clinic-pathological characteristics. TNC mRNA in situ hybridization was then used to identify the cells that express TNC within glomeruli. TNC was also tested on mouse mesangial cells (SV40 MES13) in vitro to determine its effect on mesangial cells.
TNC was found in the mesangial area of IgAN as well as fibrotic areas. A correlation study revealed that higher mesangial TNC was related to more proteinuria, a lower estimated glomerular filtration rate, and more significant clinical abnormalities (MEST score). TNC mRNA expression was shown to be prominent in the afflicted glomeruli of IgAN, but not in the minimal change disease, according to in situ hybridization. Furthermore, TNC mRNA co-localized with PDGFRβ mRNA but not with PODXL mRNA, indicating that TNC mRNA was present in glomerular mesangial cells in IgAN. Exogenous TNC increased matrix protein synthesis and mesangial cell proliferation in vitro, which was inhibited by an epidermal growth factor receptor inhibitor.
Taken together, the findings indicated that TNC produced from mesangial cells contributes to mesangial matrix growth and proliferation, which is a potential therapeutic target in IgAN.
Reference: onlinelibrary.wiley.com/doi/10.1111/nep.14031
