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Regulation of the gap junction interplay during postnatal development in the rat epididymis. 大鼠附睾产后发育过程中间隙连接相互作用的调控
IF 3.2 3区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-16 DOI: 10.1007/s00441-024-03919-1
Daniel G Cyr, Cécile Adam, Julie Dufresne, Mary Gregory

During postnatal development of the rat epididymis, a change in the expression of gap junction proteins, or connexins (Cxs), occurs, in which Gjb2 (Cx26) and Gja1 (Cx43) levels in the proximal epididymis are decreased, while Gjb1 (Cx32), Gjb4 (Cx30.3) and Gjb5 (Cx31.1) levels increase. The mechanism(s) responsible for the switch in Cx expression is unknown. The aim of this study is to identify the mechanisms responsible for the decrease in GJB2 protein levels and the increase in other Cxs during postnatal development. Results indicate that decreased Gjb2 expression for 48 h does not alter the expression of other Cxs in RCE-1 principal cells, suggesting a lack of compensatory expression. Sequence analysis of both Gjb2 and Gjb1 promoters identified common multiple response elements to steroid hormones. Using RCE-1 cells, we observed that dexamethasone increased Gjb2 mRNA levels by twofold after 48 h, while estradiol had no effect. Orchidectomy in rats resulted in a significant increase in GJB2 and decreased GJB1 in the caput and corpus epididymidis. Changes in Cxs protein levels were prevented by testosterone in orchidectomized rats. Similar results were observed in the prostate, another androgen-receptive organ. LNCaP cells, which are androgen-responsive, showed that exogenous dihydrotestosterone (DHT) decreased Gjb2 mRNA levels by approximately 50% concomitant with a 1.5-fold increase in Gjb1 levels. Using a GJB1 promoter construct we showed that DHT could induce transactivation of the luciferase transgene, while transactivation of two GJB2 promoters were unaltered. Results indicate that androgens and glucocorticoids regulate the expression of epididymal Cxs.

在大鼠附睾的产后发育过程中,间隙连接蛋白或连接蛋白(Cxs)的表达发生了变化,其中附睾近端 Gjb2(Cx26)和 Gja1(Cx43)的水平下降,而 Gjb1(Cx32)、Gjb4(Cx30.3)和 Gjb5(Cx31.1)的水平上升。导致 Cx 表达变化的机制尚不清楚。本研究的目的是确定导致出生后发育过程中 GJB2 蛋白水平下降和其他 Cx 水平上升的机制。结果表明,Gjb2表达减少48小时并不会改变RCE-1主细胞中其他Cx的表达,这表明缺乏代偿性表达。对 Gjb2 和 Gjb1 启动子的序列分析发现了对类固醇激素的共同多重反应元件。通过使用 RCE-1 细胞,我们观察到地塞米松能在 48 小时后将 Gjb2 mRNA 水平提高两倍,而雌二醇则没有影响。大鼠睾丸切除术导致睾帽和附睾中的 GJB2 显著增加,GJB1 减少。睾丸切除大鼠体内的睾酮可阻止 Cxs 蛋白水平的变化。在另一个雄激素敏感器官前列腺中也观察到了类似的结果。具有雄激素反应性的 LNCaP 细胞显示,外源性双氢睾酮(DHT)使 Gjb2 mRNA 水平降低了约 50%,同时 Gjb1 水平增加了 1.5 倍。使用 GJB1 启动子构建物,我们发现 DHT 可以诱导荧光素酶转基因的转录活化,而两个 GJB2 启动子的转录活化没有改变。结果表明,雄激素和糖皮质激素能调节附睾Cxs的表达。
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引用次数: 0
Type 2 vomeronasal receptor expression in the olfactory organ of African lungfish, Protopterus annectens. 非洲肺鱼(Protopterus annectens)嗅觉器官中 2 型绒毛膜受体的表达。
IF 3.2 3区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-09-30 DOI: 10.1007/s00441-024-03918-2
Shoko Nakamuta, Zicong Zhang, Masato Nikaido, Takuya Yokoyama, Yoshio Yamamoto, Nobuaki Nakamuta

The olfactory organ of tetrapods, with few exceptions, comprises the main and accessory organs: olfactory epithelium (OE) and vomeronasal organ (VNO). Unlike tetrapods, teleost fish lack a VNO. However, lungfish, a type of sarcopterygian fish closely related to tetrapods, possesses a lamellar OE similar to the OE of teleosts and a recess epithelium (RecE) resembling the amphibian VNO. The RecE has been hypothesized as a primordial VNO. Olfactory receptors in tetrapods are distinctively expressed in the OE and VNO. For instance, type 2 vomeronasal receptors (V2Rs) in Xenopus are categorized into those exclusively expressed in the OE and those solely expressed in the VNO. It remains unclear whether V2Rs are differentially expressed between the lamellar OE and RecE in lungfish. This study investigated V2R expression in the lamellar OE and RecE of the African lungfish, Protopterus annectens. P. annectens V2Rs were categorized into three groups: those exclusively expressed in the lamellar OE, those exclusively expressed in the RecE, and those expressed in both the lamellar OE and RecE. V2Rs exclusively expressed in the RecE and those expressed in both the lamellar OE and RecE formed a distinct clade in the phylogenetic tree, whereas others were solely expressed in the lamellar OE. These findings suggest that lungfish V2R expression represents an intermediate stage toward complete segregation between V2Rs expressed in the OE and those expressed in the VNO.

除少数例外,四足动物的嗅觉器官包括主器官和附属器官:嗅上皮(OE)和绒毛器官(VNO)。与四足动物不同,长臂猿鱼类缺乏 VNO。然而,与四足类亲缘关系密切的一种石首鱼类--肺鱼却拥有与远足类嗅觉上皮相似的片状嗅觉上皮(OE)和与两栖类嗅觉器官相似的凹陷上皮(RecE)。RecE 被假定为原始的 VNO。四足动物的嗅觉受体在 OE 和 VNO 中的表达方式各不相同。例如,章鱼的 2 型犁鼻器受体(V2Rs)可分为仅在 OE 中表达的受体和仅在 VNO 中表达的受体。目前仍不清楚 V2Rs 是否在肺鱼的片状 OE 和 RecE 中有不同的表达。本研究调查了V2R在非洲肺鱼Protopterus annectens的片状OE和RecE中的表达。研究人员将非洲肺鱼的 V2R 分成三类:只在片状 OE 中表达的 V2R、只在 RecE 中表达的 V2R 和同时在片状 OE 和 RecE 中表达的 V2R。在系统发生树中,只在RecE中表达的V2R以及同时在片状OE和RecE中表达的V2R形成了一个独特的支系,而其他V2R则只在片状OE中表达。这些发现表明,肺鱼 V2R 的表达代表了在 OE 中表达的 V2R 与在 VNO 中表达的 V2R 之间完全分离的中间阶段。
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引用次数: 0
Inhibition of BCAT1 expression improves recurrent miscarriage by regulating cellular dysfunction and inflammation of trophoblasts. 抑制BCAT1的表达可通过调节滋养细胞的细胞功能障碍和炎症改善复发性流产。
IF 3.2 3区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-10-02 DOI: 10.1007/s00441-024-03921-7
Guangli Xu, Chao Tian, Yanru Li, Lei Fang, Jing Wang, Zhuqing Jing, Simeng Li, Ping Chen

Sustained or chronic inflammation in the placenta can result in placental insufficiency, leading to adverse reproductive outcomes such as pregnancy loss. Branched-chain amino acid transaminase 1 (BCAT1) expresses in the placenta and is involved in the pathological inflammatory response, but its role in recurrent miscarriage (RM) has not been fully investigated. In the present study, we delved into the effects of BCAT1 on trophoblast inflammation induced by lipopolysaccharide (LPS) and a mouse model of pregnancy loss induced by LPS. In vitro, after the HTR-8/SVneo cells were treated with LPS and BCATc inhibitor 2 (a selective BCAT inhibitor), the cell apoptosis was verified by TUNEL assay, and the activity of caspase-3 and caspase-9 was detected. Real-time PCR, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence (IF) were used to determine the expression of inflammatory cytokines (TNF-α, IL-6, and IL-1β) and inflammasomes (NLRP3 and ASC) in LPS-treated trophoblast cells. Western blot analysis was performed to verify the expression of phospho-IκBα (p-IκBα) in cells and NF-κB p65 in the nuclei. IF staining was used to detect the nuclear translocation of NF-κB p65. The DNA binding activity of NF-κB was detected by an electrophoretic mobility shift assay (EMSA). The results demonstrated that inhibition of BCAT1 reduced trophoblast apoptosis, suppressed the release of proinflammatory cytokines, and prevented NLRP3 inflammasome activation in response to LPS. Additionally, BCAT1 inhibition blocked the activation of the NF-κB pathway in trophoblasts. This study highlights the potential therapeutic role of targeting BCAT1 in preventing adverse reproductive outcomes associated with chronic placental inflammation.

胎盘中的持续或慢性炎症可导致胎盘功能不全,从而导致不良的生殖结局,如妊娠失败。支链氨基酸转氨酶1(BCAT1)在胎盘中表达并参与病理性炎症反应,但其在复发性流产(RM)中的作用尚未得到充分研究。在本研究中,我们深入研究了BCAT1对脂多糖(LPS)诱导的滋养细胞炎症和LPS诱导的小鼠妊娠丢失模型的影响。在体外,用LPS和BCATc抑制剂2(一种选择性BCAT抑制剂)处理HTR-8/SVneo细胞后,用TUNEL试验验证细胞凋亡,并检测caspase-3和caspase-9的活性。实时 PCR、酶联免疫吸附试验(ELISA)和免疫荧光(IF)被用来检测 LPS 处理的滋养层细胞中炎性细胞因子(TNF-α、IL-6 和 IL-1β)和炎性体(NLRP3 和 ASC)的表达。进行了 Western 印迹分析以验证细胞中磷酸化-IκBα(p-IκBα)和细胞核中 NF-κB p65 的表达。IF 染色用于检测 NF-κB p65 的核转位。电泳迁移试验(EMSA)检测了 NF-κB 的 DNA 结合活性。结果表明,抑制 BCAT1 可减少滋养细胞凋亡,抑制促炎细胞因子的释放,并防止 NLRP3 炎性体在 LPS 反应中被激活。此外,抑制 BCAT1 还能阻止滋养细胞中 NF-κB 通路的激活。这项研究强调了靶向 BCAT1 在预防与慢性胎盘炎症相关的不良生殖结局方面的潜在治疗作用。
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引用次数: 0
An in-depth review of the function of RNA-binding protein FXR1 in neurodevelopment. 深入评述 RNA 结合蛋白 FXR1 在神经发育中的功能。
IF 3.2 3区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-19 DOI: 10.1007/s00441-024-03912-8
Natasha M Méndez-Albelo, Soraya O Sandoval, Zhiyan Xu, Xinyu Zhao

FMR1 autosomal homolog 1 (FXR1) is an RNA-binding protein that belongs to the Fragile X-related protein (FXR) family. FXR1 is critical for development, as its loss of function is intolerant in humans and results in neonatal death in mice. Although FXR1 is expressed widely including the brain, functional studies on FXR1 have been mostly performed in cancer cells. Limited studies have demonstrated the importance of FXR1 in the brain. In this review, we will focus on the roles of FXR1 in brain development and pathogenesis of brain disorders. We will summarize the current knowledge in FXR1 in the context of neural biology, including structural features, isoform diversity and nomenclature, expression patterns, post-translational modifications, regulatory mechanisms, and molecular functions. Overall, FXR1 emerges as an important regulator of RNA metabolism in the brain, with strong implications in neurodevelopmental and psychiatric disorders.

FMR1 常染色体同源物 1(FXR1)是一种 RNA 结合蛋白,属于脆性 X 相关蛋白(FXR)家族。FXR1 对人体发育至关重要,因为人类无法容忍其功能缺失,而小鼠则会导致新生儿死亡。虽然 FXR1 在大脑等部位广泛表达,但有关 FXR1 的功能研究大多是在癌细胞中进行的。有限的研究证明了 FXR1 在大脑中的重要性。在本综述中,我们将重点讨论 FXR1 在大脑发育和脑部疾病发病机制中的作用。我们将从神经生物学的角度总结目前有关 FXR1 的知识,包括结构特征、同工酶多样性和命名、表达模式、翻译后修饰、调控机制和分子功能。总之,FXR1 是大脑中 RNA 代谢的重要调控因子,对神经发育和精神疾病具有重要影响。
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引用次数: 0
Spatial arrangement, polarity, and posttranslational modifications of the microtubule system in the Drosophila eye. 果蝇眼睛中微管系统的空间排列、极性和翻译后修饰。
IF 3.2 3区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-17 DOI: 10.1007/s00441-024-03914-6
Piotr Kos, Otto Baumann

We have analyzed the organization of the microtubule system in photoreceptor cells and pigment cells within the adult Drosophila compound eye. Immunofluorescence localization of tubulin and of Short stop, a spectraplakin that has been reported to be involved in the anchorage of microtubule minus ends at the membrane, suggests the presence of non-centrosomal microtubule-organizing centers at the distal tip of the visual cells. Ultrastructural analyses confirm that microtubules emanate from membrane-associated plaques at the site of contact with cone cells and that all microtubules are aligned in distal-proximal direction within the photoreceptor cells. Determination of microtubule polarities demonstrated that about 95% of the microtubules in photoreceptor cells are oriented with their plus end in the direction of the synapse. Pigment cells in the eye contain only microtubules aligned in distal-proximal direction, with their plus end pointing towards the retinal floor. There, two populations of microtubules can be distinguished, single microtubules and bundled microtubules, the latter associated with actin filaments. Whereas microtubules in both photoreceptor cells and pigment cells are acetylated and mono/bi-glutamylated on α-tubulin, bundled microtubules in pigment cells are apparently also mono/bi-glutamylated on β-tubulin, providing the possibility of binding different microtubule-associated proteins.

我们分析了成体果蝇复眼内感光细胞和色素细胞中微管系统的组织结构。微管蛋白和短停蛋白的免疫荧光定位表明,在视觉细胞的远端存在非中心体的微管组织中心。超微结构分析证实,微管从与视锥细胞接触部位的膜相关斑块中发出,而且所有微管都在感光细胞内按远近方向排列。对微管极性的测定表明,感光细胞中约有 95% 的微管的加端朝向突触方向。眼睛中的色素细胞只含有按远近方向排列的微管,其正端指向视网膜底层。在这些微管中,可以区分出两种微管:单个微管和成束微管,后者与肌动蛋白丝有关。感光细胞和色素细胞中的微管都被α-微管蛋白乙酰化和单/双谷氨酰化,而色素细胞中的成束微管显然也被β-微管蛋白单/双谷氨酰化,这为结合不同的微管相关蛋白提供了可能性。
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引用次数: 0
Comparative study on a unique architecture of the brook lamprey liver and that of the hagfish and banded houndshark liver. 关于溪灯鱼肝脏独特结构与哈吉鱼和带钩鱼肝脏结构的比较研究。
IF 3.2 3区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-10-01 DOI: 10.1007/s00441-024-03917-3
Noriaki Ota, Haruka Hirose, Yuji Yamazaki, Hideaki Kato, Kazuho Ikeo, Junri Sekiguchi, Sachie Matsubara, Hayato Kawakami, Nobuyoshi Shiojiri

Although the liver of the lamprey, a group of cyclostomes that diverged the earliest among vertebrates, has abundant bile ducts in the larval stage, which degenerate during metamorphosis, there is no comparative study on its architecture with other early diverged vertebrates in terms of the morphological evolution of vertebrate livers. The present study was undertaken to compare the characteristics of the brook lamprey liver with those of the hagfish and banded houndshark, which have the portal triad type liver architecture, and to discuss its evolution. Although the liver of the brook lamprey had two-cell cords of hepatocytes lined by sinusoids in the ammocoetes larval stage, intrahepatic bile ducts around portal veins penetrated into the liver parenchyma with convolution and gradual reduction in diameter. They also faced dilated sinusoids. The epithelial cells had characteristic intercellular spaces. These characteristics were distinct from those of bile ducts in the hagfish and banded houndshark livers. Although the liver architectures of the hagfish and banded houndshark were similar, the latter penetrated the intrahepatic bile ducts more deeply along the portal veins than the former, in which intrahepatic bile ducts were restricted near the hilum. After metamorphosis, bile ducts degenerated in brook lampreys. These data indicate that the liver architecture of the ammocoetes larva is unique in the parenchymal distribution of bile ducts, their sinusoidal facing, and morphology among extant vertebrates. The periportal distribution of intrahepatic biliary structures may have been established prior to the divergence of the cyclostomes and gnathostomes.

溪灯鱼是脊椎动物中分化最早的一类环口纲动物,虽然其肝脏在幼体阶段有丰富的胆管,并在变态过程中退化,但从脊椎动物肝脏形态演化的角度来看,目前还没有关于其肝脏结构与其他早期分化脊椎动物肝脏结构的比较研究。本研究的目的是将小溪灯鱼肝脏的特征与具有门齿三联型肝脏结构的哈氏鱼和带钩鱼的特征进行比较,并探讨其演化过程。虽然小溪灯鱼的肝脏在羊膜幼体阶段具有由肝细胞组成的两细胞索,内衬为肝窦,但门静脉周围的肝内胆管穿入肝实质,并呈卷曲状,直径逐渐缩小。它们还面临着扩张的窦道。上皮细胞具有特征性的细胞间隙。这些特征与沙丁鱼和带鱼肝脏胆管的特征截然不同。虽然石首鱼和带状猎鲨的肝脏结构相似,但后者的肝内胆管沿门静脉穿入的深度比前者更深,前者的肝内胆管被限制在肝门附近。在蜕变后,小溪灯鱼的胆管退化。这些数据表明,在现存脊椎动物中,虹彩鳉幼体的肝脏结构在胆管的实质分布、窦状走向和形态上都是独一无二的。肝内胆管结构的肝门周围分布可能在环口目和地鳖目分化之前就已经形成。
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引用次数: 0
The complex neurochemistry of the cockroach antennal heart. 蟑螂触角心脏的复杂神经化学。
IF 3.2 3区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-09-06 DOI: 10.1007/s00441-024-03915-5
Hans Agricola, Peter Bräunig

The innervation of the antennal heart of the cockroach Periplaneta americana was studied with immunocytochemical techniques on both the light and electron microscopic levels. The antennal heart is innervated by two efferent systems, both using one biogenic amine in combination with neuropeptides. In one, we found co-localization of serotonin with proctolin and allatostatin. These fibers most likely originate from paired neurons located in the suboesophageal ganglion. In the second system, we found octopamine co-localized with the short neuropeptide F. The source of this second system is dorsal unpaired median (DUM) neurons, also located in the suboesophageal ganglion. The possible effects of these neuromediators on different targets are discussed.

研究人员利用免疫细胞化学技术,在光镜和电子显微镜下对蜚蠊触角心脏的神经支配进行了研究。触角心脏由两个传出系统支配,两个系统都使用一种生物胺和神经肽。在其中一个系统中,我们发现了血清素与促泌素和动情素的共定位。这些纤维很可能来自食管下神经节的成对神经元。在第二个系统中,我们发现了章鱼胺与短神经肽 F 的共定位。第二个系统的来源是同样位于食管下神经节的背侧无配对正中神经元(DUM)。本文讨论了这些神经介质对不同靶点可能产生的影响。
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引用次数: 0
A historical perspective of Kupffer cells in the context of infection. 从历史角度看感染背景下的 Kupffer 细胞。
IF 3.2 3区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-10-11 DOI: 10.1007/s00441-024-03924-4
Carolyn T Graham, Siamon Gordon, Paul Kubes

The Kupffer cell was first discovered by Karl Wilhelm von Kupffer in 1876, labeling them as "Sternzellen." Since their discovery as the primary macrophages of the liver, researchers have gradually gained an in-depth understanding of the identity, functions, and influential role of Kupffer cells, particularly in infection. It is becoming clear that Kupffer cells perform important tissue-specific functions in homeostasis and disease. Stationary in the sinusoids of the liver, Kupffer cells have a high phagocytic capacity and are adept in clearing the bloodstream of foreign material, toxins, and pathogens. Thus, they are indispensable to host defense and prevent the dissemination of bacteria during infections. To highlight the importance of this cell, this review will explore the history of the Kupffer cell in the context of infection beginning with its discovery to the present day.

卡尔-威廉-冯-库普弗(Karl Wilhelm von Kupffer)于 1876 年首次发现库普弗细胞,并将其命名为 "Sternzellen"。自从它们作为肝脏的初级巨噬细胞被发现以来,研究人员逐渐深入了解了 Kupffer 细胞的特性、功能和影响作用,尤其是在感染中的作用。人们逐渐发现,Kupffer 细胞在体内平衡和疾病中发挥着重要的组织特异性功能。Kupffer 细胞固定在肝窦中,具有很强的吞噬能力,善于清除血液中的异物、毒素和病原体。因此,它们是宿主防御和防止感染时细菌扩散所不可或缺的。为了突出这种细胞的重要性,本综述将探讨 Kupffer 细胞从发现至今在感染方面的历史。
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引用次数: 0
Diabetes compromises tight junction protein claudin 14 in the urinary bladder. 糖尿病会损害膀胱中的紧密连接蛋白 Claudin 14。
IF 3.2 3区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-20 DOI: 10.1007/s00441-024-03908-4
Soumitra Mohanty, John Kerr White, Andrea Scheffschick, Berenice Fischer, Anuj Pathak, Jonas Tovi, Claes-Göran Östenson, Pontus Aspenström, Hanna Brauner, Annelie Brauner

Infections are common in patients with diabetes. Moreover, increasing incidence of antibiotic resistance impedes the complete bacterial clearance and calls for alternative treatment strategies. Along with antibacterial resistance, compromised host conditions create a favorable condition for the disease progression. In particular, cell junction proteins are of major importance as they contribute to a tight cell barrier, protecting against invading pathogens. However, the impact of high glucose on cell junction proteins has received little attention in the urinary bladder but merits closer investigation. Here, we report that during diabetes the expression of cell junction protein, claudin 14 is compromised in the human urine exfoliated cells and in the urinary bladder of type 2 diabetic mouse. Further in vitro analysis confirmed a direct correlation of lower intracellular calcium levels with claudin 14 expression in high glucose-treated human uroepithelial cells. Moreover, external calcium supplementation in high glucose-treated cells significantly affected the cell migration and restored the claudin 14 expression through focal adhesion and β-1 integrins. Strengthening the epithelial barrier is essential, especially in individuals with diabetes where basal calcium levels could contribute.

感染是糖尿病患者的常见病。此外,抗生素耐药性的增加阻碍了细菌的彻底清除,因此需要采取其他治疗策略。除了抗菌药耐药性,宿主条件受损也为疾病的发展创造了有利条件。细胞连接蛋白尤其重要,因为它们有助于形成严密的细胞屏障,抵御病原体的入侵。然而,在膀胱中,高血糖对细胞连接蛋白的影响很少受到关注,但值得进行更深入的研究。在这里,我们报告了在糖尿病期间,细胞连接蛋白 Claudin 14 在人尿脱落细胞和 2 型糖尿病小鼠膀胱中的表达受到影响。进一步的体外分析证实,在高糖处理的人类尿路上皮细胞中,细胞内钙水平降低与 claudin 14 的表达直接相关。此外,在高糖处理的细胞中补充外部钙,可显著影响细胞迁移,并通过局灶粘附和β-1整合素恢复claudin 14的表达。加强上皮屏障非常重要,尤其是对基础钙水平较低的糖尿病患者而言。
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引用次数: 0
Involvement of vimentin- and BLBP-positive glial cells and their MMP expression in axonal regeneration after spinal cord transection in goldfish. 波形蛋白和 BLBP 阳性神经胶质细胞及其 MMP 表达参与金鱼脊髓横断后的轴突再生
IF 3.2 3区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-09 DOI: 10.1007/s00441-024-03907-5
Akihito Takeda, Minami Teshima, Kengo Funakoshi

In goldfish, spinal cord injury triggers the formation of a fibrous scar at the injury site. Regenerating axons are able to penetrate the scar tissue, resulting in the recovery of motor function. Previous findings suggested that regenerating axons enter the scar through tubular structures surrounded by glial elements with laminin-positive basement membranes and that glial processes expressing glial fibrillary acidic protein (GFAP) are associated with axonal regeneration. How glia contribute to promoting axonal regeneration, however, is unknown. Here, we revealed that glial processes expressing vimentin or brain lipid-binding protein (BLBP) also enter the fibrous scar after spinal cord injury in goldfish. Vimentin-positive glial processes were more numerous than GFAP- or BLBP-positive glial processes in the scar tissue. Regenerating axons in the scar tissue were more closely associated with vimentin-positive glial processes than GFAP-positive glial processes. Vimentin-positive glial processes co-expressed matrix metalloproteinase (MMP)-14. Our findings suggest that vimentin-positive glial processes closely associate with regenerating axons through tubular structures entering the scar after spinal cord injury in goldfish. In intact spinal cord, ependymo-radial glial cell bodies express BLBP and their radial processes express vimentin, suggesting that vimentin-positive glial processes derive from migrating ependymo-radial glial cells. MMP-14 expressed in vimentin-positive glial cells and their processes might provide a beneficial environment for axonal regeneration.

在金鱼身上,脊髓损伤会在损伤部位形成纤维疤痕。再生轴突能够穿透疤痕组织,从而恢复运动功能。以前的研究结果表明,再生轴突通过被具有层粘连蛋白阳性基底膜的胶质细胞包围的管状结构进入疤痕,而表达胶质纤维酸性蛋白(GFAP)的胶质过程与轴突再生有关。然而,神经胶质如何促进轴突再生尚不清楚。在这里,我们发现金鱼脊髓损伤后,表达波形蛋白或脑脂质结合蛋白(BLBP)的胶质过程也会进入纤维瘢痕。在疤痕组织中,波形蛋白阳性的神经胶质过程比 GFAP 或 BLBP 阳性的神经胶质过程更多。与 GFAP 阳性神经胶质过程相比,疤痕组织中再生轴突与波形蛋白阳性神经胶质过程的关系更为密切。波形蛋白阳性的胶质过程共同表达基质金属蛋白酶(MMP)-14。我们的研究结果表明,在金鱼脊髓损伤后,波形蛋白阳性胶质过程与通过管状结构进入瘢痕的再生轴突密切相关。在完整的脊髓中,脊髓外侧神经胶质细胞体表达 BLBP,其径向过程表达波形蛋白,这表明波形蛋白阳性的神经胶质过程来自迁移的脊髓外侧神经胶质细胞。在波形蛋白阳性胶质细胞及其过程中表达的MMP-14可能为轴突再生提供了有利的环境。
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Cell and Tissue Research
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