Cardiac Wnt5a and Wnt11 promote fibrosis by the crosstalk of FZD5 and EGFR signaling under pressure overload

Progressive cardiac fibrosis accelerates the development of heart failure. Here, we aimed to explore serum Wnt5a and Wnt11 levels in hypertension patients, the roles of Wnt5a and Wnt11 in cardiac fibrosis and potential mechanisms under pressure overload. The pressure overload mouse model was built by transverse aortic constriction (TAC). Cardiac fibrosis was analyzed by Masson’s staining. Serum Wnt5a or Wnt11 was elevated and associated with diastolic dysfunction in hypertension patients. TAC enhanced the expression and secretion of Wnt5a or Wnt11 from cardiomyocytes (CMs), cardiac fibroblasts (CFs), and cardiac microvascular endothelial cells (CMECs). Knockdown of Wnt5a and Wnt11 greatly improved cardiac fibrosis and function at 4 weeks after TAC. In vitro, shWnt5a or shWnt11 lentivirus transfection inhibited pro-fibrotic effects in CFs under mechanical stretch (MS). Similarly, conditional medium from stretched-CMs transfected with shWnt5a or shWnt11 lentivirus significantly suppressed the pro-fibrotic effects induced by conditional medium from stretched-CMs. These data suggested that CMs- or CFs-derived Wnt5a or Wnt11 showed a pro-fibrotic effect under pressure overload. In vitro, exogenous Wnt5a or Wnt11 activated ERK and p38 (fibrotic-related signaling) pathway, promoted the phosphorylation of EGFR, and increased the expression of Frizzled 5 (FZD5) in CFs. Inhibition or knockdown of EGFR greatly attenuated the increased FZD5, p-p38, and p-ERK levels, and the pro-fibrotic effect induced by Wnt5a or Wnt11 in CFs. Si-FZD5 transfection suppressed the increased p-EGFR level, and the fibrotic-related effects in CFs treated with Wnt5a or Wnt11. In conclusion, pressure overload enhances the secretion of Wnt5a or Wnt11 from CMs and CFs which promotes cardiac fibrosis by activation the crosstalk of FZD5 and EGFR. Thus, Wnt5a or Wnt11 may be a novel therapeutic target for the prevention of cardiac fibrosis under pressure overload.Subject terms: Heart failure, Translational research     

两种除草剂对棉田节肢动物群落多样性指数的影响

系统地研究了棉田地面和棉株节肢动物群落及各亚群落施用克无踪(A)、高盖(B)与对照(CK)之间在群落生物多样性、丰富度和均匀度的差异.结果表明,对地面肉食动物群落生物多样性(H′)的A-CK的t值为3.099,B-CK的t值为2.449,t＞t_0.05=2.228,差异显著;地面植食动物亚群落的(H′)A-CK的t值为2.377,A-B为2.260,t＞t_0.05=2.228,差异均显著.棉株节肢动物群落及亚群落A-CK、B-CK和A-B之间差异不显著.地面节肢动物亚群落丰富度A-CK的t值为4.759,地面植食类节肢动物亚群落为4.359,地面肉食节肢动物亚群落为2.963,均t＞t0.0=2.228,表明A与CK之间差异显著;在均匀度上,A和B及A-CK、B与CK之间两类群落及亚群落上差异均不显著.A和B对棉株节肢动物群落影响很小.施用A和B及CK的生物多样性的变化总趋势一致.     

后基因组时代基因功能分析的策略

人类基因组计划的完成标志着生命科学已经开始迈进后基因组时代,大规模基因的功能研究正成为生命科学研究的热点。基因功能的分析方法日趋成熟和多样化,综述了基因敲除、反义技术、“dominantnegative”策略(“显性失活”策略)、基因诱导超表达、RNA干涉以及生物信息学等基因功能分析策略的特异性及其优缺点。     

抗冻蛋白研究进展

抗冻蛋白是一类具有热滞效应、冰晶形态效应和重结晶抑制效应的蛋白质。简单介绍了各种抗冻蛋白的生化特征、作用机制及其应用研究 ,并对抗冻蛋白的基因和基因工程研究作了较为系统的综述。     

A heparin-binding growth factor, midkine, binds to a chondroitin sulfate proteoglycan, PG-M/versican.

Midkine is a heparin-binding growth factor with survival-promoting and migration-enhancing activities. In order to understand the regulation of midkine signaling, we isolated midkine-binding proteoglycans from day 13 mouse embryos, when midkine is intensely expressed. Deglycosylation followed by SDS/PAGE revealed various protein bands; one of these was identified as PG-M/versican by in gel trypsin digestion and sequencing the resulting peptides. PG-M/versican isolated from day 13 mouse embryos bound midkine with a Kd of 1.0 nM. Pleiotrophin/heparin-binding growth-associated molecule, which has a structure related to midkine, was also bound similarly. Digestion with chondroitinase ABC, AC-I or B abolished the binding to midkine. Heparin as well as chondroitin sulfate D and E inhibited the binding. After chondroitinase ABC digestion, the midkine-binding PG-M/versican released 4-sulfated, 6-sulfated, 2, 6-disulfated and 4,6-disulfated unsaturated disaccharides. These results suggest that midkine binds to a polysulfated domain in the chondroitin sulfate chain with a region of dermatan sulfate structure. This proteoglycan may modulate the midkine activity, as binding to midkine can enhance midkine action by concentrating it to the cell periphery or inhibit the action by competing with the binding to a signaling receptor.     

IL1RN promotes osteoblastic differentiation via interacting with ITGB3 in osteoporosis

The occurrence and progress of osteoporosis(OP)are partially caused by impaired osteoblast differentiation.Interleukin-I receptor antagonist(IL1RN)is an immune ...     

放牧对鄂尔多斯高原油蒿草场生物量及植被-土壤碳密度的影响

以围封保护和自由放牧油蒿草场为研究对象,通过野外调查与室内分析,研究了围封和放牧条件下沙地草场生物量和植被-土壤碳密度。结果表明:(1)自由放牧使油蒿群落中植物种类增加,但降低了植物群落盖度。自由放牧不仅导致油蒿草场地上、地下总生物量降低,也使得油蒿地上、地下生物量占群落地上、地下总生物量的比例减小。生长季自由放牧样地凋落物生物量显著大于围封保护样地(P0.05);(2)围封保护样地植被碳密度大于自由放牧样地,土壤碳密度却小于自由放牧样地,但两个样地间差异不显著(P0.05);(3)油蒿草场90%以上的碳储存于土壤中,围封保护样地和自由放牧样地油蒿草场土壤碳密度占植被-土壤系统碳密度的91%、93%;(4)围封保护油蒿草场碳密度为2.29 kg/m2,自由放牧油蒿草场碳密度为2.68 kg/m2,两个样地间差异不显著,自由放牧对油蒿草场碳密度影响不大。     

粘虫迁飞能源物质的研究

粘虫具有迁飞特性。本研究对迁飞型和居留型的粘虫雌、雄蛾进行生理测定,分别分析了虫体糖原、总脂肪含量,并对虫体腹腔内脂肪体显微切片进行组织学观察,其结果表明,脂肪是粘虫迁飞的主要能源物质。     

Alternatively activated macrophages at the recipient site improve fat graft retention by promoting angiogenesis and adipogenesis

The inflammatory response mediated by macrophages plays a role in tissue repair. Macrophages preferentially infiltrate the donor site and subsequently, infiltrate the recipient site after fat grafting. This study aimed to trace host‐derived macrophages and to evaluate the effects of macrophage infiltration at the recipient site during the early stage on long‐term fat graft retention. In our novel mouse model, all mice underwent simulated liposuction and were divided into 2 groups. The fat procurement plus grafting (Pro‐Grafting) group was engrafted with prepared fat (0.3 ml). The pro‐Grafting+M2 group was engrafted with prepared fat (0.3 ml) mixed with 1.0 × 10⁶ GFP+M0 macrophages, and then, 2 ng IL‐4 was injected into the grafts on Day 3. In addition, 1.0 × 10⁶ GFP+M0 macrophages were injected into the tail vein for tracing in the Pro‐Grafting group. As a result, GFP+macrophages first infiltrated the donor site and subsequently infiltrated the recipient site in the Pro‐Grafting group. The long‐term retention rate was higher in the Pro‐Grafting+M2 group (52% ± 6.5%) than in the Pro‐Grafting group (40% ± 3.5%). CD34+ and CD31+ areas were observed earlier, and expression of the adipogenic proteins PPAR‐γ, C/EBP and AP2 was higher in the Pro‐Grafting+M2 group than in the Pro‐Grafting group. The host macrophages preferentially infiltrate the donor site, and then, infiltrate the recipient site after fat grafting. At the early stage, an increase in macrophages at the recipient site may promote vascularization and regeneration, and thereby improve the fat graft retention rate.