cyclin-d1 and Glomerulonephritis--IGA

IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. However, the etiology of this disease is complex and the pathogenesis of IgAN is still unknown. MicroRNAs (miRNAs) play important roles in a lot of pathological and physiological processes. In this study, we showed that the expression of miR-320 was significantly upregulated in renal tissues and urinary of IgAN patients. Moreover, the intra-renal expression level of miR-320 had significant correlation with miR-320 expression in the urinary of IgAN patients. Overexpression of miR-320 increased B cell proliferation and promoted cyclin D1 expression. Furthermore, we identified that PTEN was direct target gene of miR-320 in the B cell. Ectopic expression of miR-320 suppressed PTEN expression. Overexpression of miR-320 decreased Cosmc expression in the B cell. In addition, we demonstrated that Cosmc expression was significantly downregulated in the renal tissues and urinary of IgAN patients. The intra-renal expression level of Cosmc had significant correlation with Cosmc expression of urinary in IgAN patients. We proved that the expression level of Cosmc was negatively correlated with the expression of miR-320 in the renal tissues of IgAN patients. Overexpression of miR-320 promoted the B cell proliferation through suppressing PTEN expression. Taken together, these data suggested that miR-320 acted an important role in the development of IgAN.

Topics: B-Lymphocytes; Cell Line; Cell Proliferation; Cyclin D1; Gene Expression Regulation; Glomerulonephritis, IGA; Humans; Immunoglobulin A; Kidney; MicroRNAs; Molecular Chaperones; PTEN Phosphohydrolase

IgA nephropathy (IgAN) has been considered to be the most frequent form of primary glomerulonephritis that occurs worldwide with a variety of factors involved in its occurrence and development. The impact of autophagy in IgAN, however, remains partially unclear. This study was designed to investigate the effects of rapamycin in an IgAN model.. After establishing an IgAN rat model, SD rats were divided into 4 groups: control, control + rapamycin, IgAN, IgAN + rapamycin. Proteinuria and the pathological changes and the level of autophagy of kidney were texted. Identify the expression of phosphorylation and total mammalian target of rapamycin (mTOR) and s6k1 as well as cyclin D1 in the kidney of rats through Western blot and immunohistochemistry.. With rapamycin treatment, we observed a significant reduction in the progression of proteinuria as well as alleviation of pathological lesions in IgAN rats. Besides, autophagy was inhibited, while the mTOR/S6k1 pathway was activated and expression of cyclin D1 was increased in IgAN. Rapamycin treatment increased autophagy and decreased the expression of cyclin D1.. These results may suggest that mTOR-mediated autophagy inhibition may result in mesangial cell proliferation in IgAN.

Topics: Animals; Autophagy; Cell Proliferation; Cyclin D1; Disease Models, Animal; Glomerulonephritis, IGA; Humans; Immunohistochemistry; Immunosuppressive Agents; Mesangial Cells; Microscopy, Electron; Proteinuria; Rats; Rats, Sprague-Dawley; Ribosomal Protein S6 Kinases; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases