| First Author | Shotorbani PY | Year | 2020 |
| Journal | Am J Physiol Renal Physiol | Volume | 318 |
| Issue | 3 | Pages | F673-F682 |
| PubMed ID | 31984795 | Mgi Jnum | J:294303 |
| Mgi Id | MGI:6451206 | Doi | 10.1152/ajprenal.00508.2019 |
| Citation | Shotorbani PY, et al. (2020) Inhibitor of myogenic differentiation family isoform a, a new positive regulator of fibronectin production by glomerular mesangial cells. Am J Physiol Renal Physiol 318(3):F673-F682 |
| abstractText | Overproduction of extracellular matrix proteins, including fibronectin by mesangial cells (MCs), contributes to diabetic nephropathy. Inhibitor of myogenic differentiation family isoform a (I-mfa) is a multifunctional cytosolic protein functioning as a transcriptional modulator or plasma channel protein regulator. However, its renal effects are unknown. The present study was conducted to determine whether I-mfa regulated fibronectin production by glomerular MCs. In human MCs, overexpression of I-mfa significantly increased fibronectin abundance. Silencing I-mfa significantly reduced the level of fibronectin mRNA and blunted transforming growth factor-beta1-stimulated production of fibronectin. We further found that high glucose increased I-mfa protein content in a time course (>/=48 h) and concentration (>/=25 mM)-dependent manner. Although high glucose exposure increased I-mfa at the protein level, it did not significantly alter transcripts of I-mfa in MCs. Furthermore, the abundance of I-mfa protein was significantly increased in the renal cortex of rats with diabetic nephropathy. The I-mfa protein level was also elevated in the glomerulus of mice with diabetic kidney disease. However, there was no significant difference in glomerular I-mfa mRNA levels between mice with and without diabetic nephropathy. Moreover, H2O2 significantly increased I-mfa protein abundance in a dose-dependent manner in cultured human MCs. The antioxidants polyethylene glycol-catalase, ammonium pyrrolidithiocarbamate, and N-acetylcysteine significantly blocked the high glucose-induced increase of I-mfa protein. Taken together, our results suggest that I-mfa, increased by high glucose/diabetes through the production of reactive oxygen species, stimulates fibronectin production by MCs. |
