Binghai Zhao

Diabetic nephropathy is characterized by persistent albuminuria, progressive decline in GFR, and secondary hypertension. MicroRNAs are dysregulated in diabetic nephropathy, but identification of the specific microRNAs involved remains incomplete. Here, we show that the peripheral blood from patients with diabetes and the kidneys of animals with type 1 or 2 diabetes have low levels of microRNA-25 (miR-25) compared with those of their nondiabetic counterparts. Furthermore, treatment with high glucose decreased the expression of miR-25 in cultured kidney cells. In db / db mice, systemic administration of an miR-25 agomir repressed glomerular fibrosis and reduced high BP. Notably, knockdown of miR-25 in normal mice by systemic administration of an miR-25 antagomir resulted in increased proteinuria, extracellular matrix accumulation, podocyte foot process effacement, and hypertension with renin-angiotensin system activation. However, excessive miR-25 did not cause kidney dysfunction in wild-type mice. RNA sequencing showed the alteration of miR-25 target genes in antagomir-treated mice, including the Ras-related gene CDC42. In vitro , cotransfection with the miR-25 antagomir repressed luciferase activity from a reporter construct containing the CDC42 3′ untranslated region. In conclusion, these results reveal a role for miR-25 in diabetic nephropathy and indicate a potential novel therapeutic target for this disease.

To explore the effects of testosterone synthesis in adult leydig cell (ALC) of male rats exposed by perfluorooctane sulfonate (PFOS) during pregnancy. At gestations 12 day, the pregnant rats were exposed to PFOS (5 mg/kg, PFOS group) or 0.5% Tween (control group) by gavage, once a day for 8 consecutive days. On postnatal day (PND) 70, several indexes of male offspring rats were measured including body mass, testicular coefficient, sperm count, serum testosterone concentration. The mRNA levels of ALC associated with testosterone synthesis were detected by real-time quantitative RT-PCR. The result showed that sperm count and serum testosterone concentration decreased in male offspring rats of PFOS group (P < 0.05), and body mass was significantly lower (P < 0.001). The expression of steroidogenic acute regulatory factor (Star), scavenger receptor class B type 1 (Scarb1), Cyp11a1 (coding gene of cytochrome P450 side chain cleavage) and Hsd17b3 (coding gene of 17β-hydroxysteroid dehydrogenase) were down regulated (P < 0.05), no significant statistical difference was observed on the mRNA level of insulin-like growth factor-1 (Igf1) and insulin-like factor 3 (Insl3). Gestational exposure to PFOS can inhibit the mRNA levels associated with testosterone synthesis, and decrease the ability of testosterone synthesis in ALC of male offspring rats.

Serum testosterone levels have been found lower in acute ischemic stroke male patients. However, the exact mechanism remains unclear. In the present study, we measured serum testosterone levels, steroidogenesis- related genes and Leydig cells number in experimental transient cerebral ischemia male rats to elucidate the mechanism. The middle cerebral arteries of adult male Sprague-Dawley rats were sutured for 120 minutes and then sacrificed after 24 hours. Blood was collected for measurement of serum testosterone, follicular stimulating hormone and estradiol levels, and testes were collected for measurement of steroidogenesis-related gene mRNA levels and number of Leydig cells. Serum testosterone levels in rats after cerebral ischemia were significantly lower (0.53 ± 0.16) ng/ml, n = 7, mean ± SE) compared with control ((2.33 ± 0.60) ng/ml, n = 7), while serum estradiol and follicular stimulating hormone levels did not change. The mRNA levels for luteinizing hormone receptor (Lhcgr), scavenger receptor class B member 1 (Scarb1), steroidogenic acute regulatory protein (StAR), cholesterol side chain cleavage enzyme (Cyp11a1), 3β-hydroxysteroid dehydrogenase 1 (HSD3β1), 17α-hydroxylase/20-lyase (Cyp17a1) and membrane receptor c-kit (kit) were significantly downregulated by cerebral ischemia, while luteinizing hormone, Kit ligand (KitL), 17β-hydrosteroid dehydrogenase 3 (HSD17β3) and 5α-reductase (Srd5a1) were not affected. We also observed that, relative to control, the Leydig cell number did not change. These results indicate that transient cerebral ischemia in the brain results in lower expression levels of steroidogenesis-related genes and thus lower serum testosterone level. Transient cerebral ischemia did not lower the number of Leydig cells.