Acute kidney injury (AKI) is a serious clinical disease that is mainly caused by renal ischemia-reperfusion (I/R) injury, sepsis, and nephrotoxic drugs. The pathologic mechanism of AKI is very complex and may involve oxidative stress, inflammatory response, autophagy, apoptosis, and endoplasmic reticulum (ER) stress. The basic fibroblast growth factor (FGF2) is a canonic member of the FGF family that plays a crucial role in various cellular processes, including organ development, wound healing, and tissue regeneration. However, few studies have reported the potential therapeutic effect of FGF2 in the repair of renal ischemic injury in the past two decades. In the present study, we investigated the protective effect of FGF2 on renal I/R injury using Sprague-Dawley and NRK-52E cells. Our results showed that FGF2 significantly attenuates the apoptosis of kidney tissues after I/R injury through the inhibition of excessive ER stress. Moreover, FGF2 also alleviated the excessive ER stress and apoptosis in cultured NRK-52E cells injured by tert-Butyl hydroperoxide (TBHP). Significantly, phosphatidylinositol 3-kinase (PI3K)-selective inhibitor LY294002 and mitogen-activated protein kinase kinase (MEK)-selective inhibitor U0126 were utilized in the present study to examine the protective mechanism of FGF2. Our in vitro experimental results confirmed that both LY294002 and U0126 largely abolished the protective effect of FGF2. Taken together, the findings of the present study indicated that FGF2 attenuates I/R-induced renal epithelial apoptosis by suppressing excessive ER stress via the activation of the PI3K/AKT and MEK-ERK1/2 signaling pathways.
In addition to women's unique diseases in reproductive organs, many other diseases also have clear gender preferences. Whether this can be explained by the unique process of Xi in women is an interesting question."
Oxygen-sensitive, voltage-gated potassium channels (Kv) may contribute to the determination of the membrane potential in smooth muscle cells of the ductus arteriosus (DA), and thus to regulation of contractile tone in response to oxygen. Developmental changes in Kv during gestation may be related to closure of the DA after birth. This study investigated developmental changes in the expression of Kv in the DA and compared it with that of the pulmonary artery (PA) and the aorta (Ao). The DA, PA, and Ao were isolated from fetal rats at days 19 and 21 of gestation (term: 21.5 days). The expression of Kv1.2, Kv1.5, Kv2.1, and Kv3.1, putative oxygen-sensitive Kv channels that open in response to oxygen, was evaluated at both the mRNA and protein levels, using quantitative real-time polymerase chain reaction and immunohistochemistry. In the Kv family studied, Kv1.5 mRNA was expressed most abundantly in the DA, PA, and Ao in both day-19 and day-21 fetuses. Although the expression levels of Kv1.2, Kv1.5, Kv2.1, and Kv3.1 did not change much with development in the PA and Ao, in the DA they decreased with development. The decrease in the expression of Kv channels may enhance DA closure after birth by eliminating the opening of Kv channels when oxygen increases.
ABSTRACT:The voltage-gated potassium channels (Kv) are partially responsible for the contraction/relaxation of blood vessels in response to changes in the PO 2 level. The present study determined the expression of Kv1 and four oxygen-sensitive Kv␣ subunits (Kv1.2, Kv1.5, Kv2.1, and Kv9.3) in the ductus arteriosus (DA), the aorta (Ao), and the pulmonary artery (PA) in porcine neonates immediately after birth. We cloned three Kv1 transcript variants (Kv1.2, Kv1.3, and Kv1.4), Kv1.2, Kv1.5, and Kv9.3 from piglets. Three Kv1 transcripts, Kv1.2, Kv1.5, and Kv9.3, encode predicted proteins of 401, 408, 202, 499, 600, and 491 residues. These Kv showed a high degree of sequence conservation with the corresponding Kv in human. Northern and quantitative real-time PCR (qr-PCR) analyses showed that Kv1.2 expression was high in the DA and Ao but low in the PA. Kv1.5 expression was high in the Ao and PA but low in the DA. Expression of Kv1.3, Kv1.4, Kv1.2, Kv2.1, and Kv9.3 was low in these blood vessels. The inactivation property of Kv1.2 against Kv1.5 was confirmed using Xenopus laevis oocytes. Our findings suggest that the molecular basis for the differential electrophysiological characteristics including opposing response to oxygen in the DA and the PA are partially due to diversity in expression of Kv1.5 and Kv1.2 subunits. The high expression of Kv1.2 and relatively low expression of Kv1.5 in the DA might be partially responsible for the ductal closure after birth.
Background Gestational diabetes mellitus (GDM) is a pregnancy-specific carbohydrate intolerance Which can cause a large number of perinatal and postpartum complications. The members of Transforming growth factor-β (TGF-β) superfamily play key roles in the homeostasis of pancreatic β-cell and may involve in the development of GDM. This study aimed to explore the association between the polymorphisms of TGF-β1, TGF-β3 and the risk to GDM in Chinese women. Methods This study included 919 GDM patients (464 with preeclampsia and 455 without preeclampsia) and 1177 healthy pregnant women. TaqMan allelic discrimination real-Time PCR was used to genotype the TGF-β1 (rs4803455) and TGF-β3 (rs2284792 and rs3917201), The Hardy-Weinberg equilibrium (HWE) was evaluated by chi-square test. Results An increased frequency of TGF-β3 rs2284792 AA and AG genotype carriers was founded in GDM patients (AA vs. AG + GG: χ2 = 6.314, P = 0.012, OR = 1.270, 95%CI 1.054–1.530; AG vs. GG + AA: χ2 = 8.545, P = 0.003, OR = 0.773, 95%CI 0.650–0.919). But there were no significant differences in the distribution of TGF-β1 rs4803455 and TGF-β3 rs3917201 between GDM and healthy women. In addition, no significant differences were found in allele and genotype frequencies among GDM patients with preeclampsia (PE). Conclusions The AA and AG genotype of TGF-β3 rs2284792 polymorphism may be significantly associated with increased risk of GDM in Chinese population.
Background/Aims: Several lines of evidence have been reported that oxidative stress plays an important role in the pathogenesis of Preeclampsia (PE). Therefore, this research is aimed to investigate whether polymorphisms of CYBA are related to susceptibility to PE in Chinese Han women. Methods: We studied the genetic frequency of the rs9932581 and 1049255 polymorphisms in CYBA in 1029 PE patients and 1400 controls of later pregnant women by the TaqMan allelic discrimination real-time PCR and a case-control model. Results: Our research indicated that no significant differences were found for the genotypic or allelic frequencies at the two polymorphic sites in CYBA between PE patients and controls. To further study the relationship between the polymorphic sites and PE, we also found that there is no significant difference in the genetic distributions identified between the mild or severe PE and early or the late-onset PE and controls. Conclusion: The study demonstrated that the genetic variants of rs9932581 and rs1049255 in CYBA might not be associated with PE. However, investigations of genetic variability that influence on the disease outcome are needed in other large prospective populations or regions, so the complicated interconnection of genetic and environmental elements can be emulated for better understanding.
Background: Gestational diabetes mellitus (GDM) is a pregnancy-specific carbohydrate intolerance Which can cause a large number of perinatal and postpartum complications. The members of Transforming growth factor-β (TGF-β) superfamily play key roles in the homeostasis of pancreatic β-cell and may involve in the development of GDM. This study aimed to explore the association between the polymorphisms of TGF-β1, TGF-β3 and the risk to GDM in Chinese women.Methods: This study included 919 GDM patients (464 with preeclampsia and 455 without preeclampsia) and 1177 healthy pregnant women. TaqMan allelic discrimination real-Time PCR was used to genotype the TGF-β1 (rs4803455) and TGF-β3 (rs2284792 and rs3917201), The Hardy-Weinberg equilibrium (HWE) was evaluated by chi-square test.Results: An increased frequency of TGF-β3 rs2284792 AA and AG genotype carriers was founded in GDM patients (AA vs. AG+GG: χ²=6.314, P=0.012, OR=1.270, 95%CI 1.054-1.530; AG vs. GG+AA: χ²=8.545, P=0.003, OR=0.773, 95%CI 0.650-0.919). But there were no significant differences in the distribution of TGF-β1 rs4803455 and TGF-β3 rs3917201 between GDM and healthy women. In addition, no significant differences were found in allele and genotype frequencies among GDM patients with preeclampsia (PE).Conclusions: The AA and AG genotype of TGF-β3 rs2284792 polymorphism may be significantly associated with increased risk of GDM in Chinese population.
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