INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 23
·14831
·
IF 6.208
Aiyun Yang,Shen Li,Yan Zhang,Xiuwei Wang,Zhen Guan,Zhiqiang Zhu,Yingchao Liang,Lijiao Zhao,Jianhua Wang
Neural-tube defects (NTDs) are one type of the most serious birth defects. Studies have shown that inositol deficiency is closely related to the occurrence of NTDs. Bone morphogenetic protein (BMP)-mediated Smad signaling pathways have been implicated in neurogenesis and neural-tube closure. However, the role of the BMP/Smad pathway in inositol-deficiency-induced NTDs remains unclear. Inositol-deficiency models in C57 mice and mouse neural stem cells (mNSCs) were induced with Li2CO3treatment or inositol withdrawal. The role of the BMP/Smad pathway in the regulation of cell proliferation and the development of NTDs was determined utilizing qRT-PCR, HE staining, Western blot, immunostaining, MTT assay, EdU staining, and flow cytometry. The intraperitoneal injection of Li2CO3at Embryonic Day 7.5 induced the occurrence of NTDs. The mRNA levels ofBmp2,Bmp4,Smad1,Smad5,Smad8andRunx2, the phosphorylation of Smad1/5/8, and the nuclear translocation of Runx2 were significantly increased in NTD embryonic brain tissues and mNSCs exposed to Li2CO3or an inositol-free medium, which were suppressed by BMP receptor selective inhibitor LDN-193189. The Li2CO3-induced phosphorylation of Smad1/5/8 was inhibited by inositol supplementation. Cell proliferation was significantly promoted by Li2CO3exposure or the absence of inositol in mNSCs, which was reversed by LDN-193189. These results suggest that the activation of the BMP/Smad signaling pathway might play an important role in the development of NTDs induced by maternal Li2CO3exposure via inositol deficiency.Keywords:inositol;BMP signaling;neural-tube defects;neural stem cell;proliferation
研究领域:
发育生物学
·
神经科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL PROLIFERATION
·
2024
·
IF 5.9
Yaqing Chen,Yi Yan,Yujing Li,Liang Zhang,Tingting Luo,Xinlong Zhu,Dan Qin,Ning Chen,Wendong Huang,Xiangmei Chen,Liqiang Wang,Xianmin Zhu,Lisheng Zhang
Transglutaminase 2 (Tgm2) plays an essential role in hepatic repair following prolonged toxic injury. During cholestatic liver injury, the intrahepatic cholangiocytes undergo dynamic tissue expansion and remodelling, referred to as ductular reaction (DR), which is crucial for liver regeneration. However, the molecular mechanisms governing the dynamics of active cells in DR are still largely unclear. Here, we generated Tgm2-knockout mice (Tgm2 −/− ) and Tgm2- CreERT2 -Rosa26-mTmG flox/flox (Tgm2 CreERT2 -R26T/G f/f ) mice and performed a three-dimensional (3D) collagen gel culture of mouse hepatocytes to demonstrate how Tgm2 signalling is involved in DR to remodel intrahepatic cholangiocytes. Our results showed that the deletion of Tgm2 adversely affected the functionality and maturity of the proliferative cholangiocytes in DR, thus leading to more severe cholestasis during DDC-induced liver injury. Additionally, Tgm2 hepatocytes played a crucial role in the regulation of DR through metaplasia. We unveiled that Tgm2 regulated H3K4me3Q5ser via serotonin to promote BMP signalling activation to participate in DR. Besides, we revealed that the activation or inhibition of BMP signalling could promote or suppress the development and maturation of cholangiocytes in DDC-induced DR. Furthermore, our 3D collagen gel culture assay indicated that Tgm2 was vital for the development of cholangiocytes in vitro. Our results uncovered a considerable role of BMP signalling in controlling metaplasia of Tgm2 hepatocytes in DR and revealed the phenotypic plasticity of mature hepatocytes.
研究领域:
肝病学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2019
·Vol. 43
·期 5
·2103-2117
·
IF 2.928
Nan Miao,Yuanbo Zhan,Yingying Xu,Haoze Yuan,Chunlin Qin,Feng Lin,Xiaohua Xie,Sen Mu,Mengtong Yuan,Haibin Mu,Shouli Guo,Ying Li,Bin Zhang
Family with sequence similarity 20‑member C (FAM20C), a recently characterized Golgi kinase, performs numerous biological functions by phosphorylating more than 100 secreted proteins. However, the role of FAM20C in the salivary glands remains undefined. The present study demonstrated that FAM20C is mainly located in the cytoplasm of duct epithelial cells in the salivary glands. Fam20cf/f; Mmtv‑Cre mice were created in which Fam20c was inactivated in the salivary gland cells and observed that the number of ducts and the ductal cross‑sectional area increased significantly, while the number of acinar cells was reduced. The granular convoluted tubules (GCTs) exhibited an accumulation of aberrant secretory granules, along with a reduced expression and altered distribution patterns of β nerve growth factor, α‑amylase and bone morphogenetic protein (BMP) 4. This abnormality suggested that the GCT cells were immature and exhibited defects in developmental and secretory functions. In accordance with the morphological alterations and the reduced number of acinar cells, FAM20C deficiency in the salivary glands significantly decreased the salivary flow rate. The Na+, Cl– and K+ concentrations in the saliva were all significantly increased due to dysfunction of the ducts. Furthermore, Fam20c deficiency significantly increased BMP2 and BMP7 expression, decreased BMP4 expression, and attenuated the canonical and noncanonical BMP signaling pathways in the salivary glands. Collectively, the results of the present study demonstrate that FAM20C is a key regulator of acinar and duct structure and duct maturation and provide a novel avenue for investigating novel therapeutic targets for oral diseases including xerostomia.
研究领域:
分子生物学
·
发育生物学
·
口腔疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2024
·
IF 7.5
Weigang Wang,Na Yang,Liangliang Wang,Yuanxiang Zhu,Xiao Chu,Weijie Xu,Yawei Li,Yihai Xu,Lina Gao,Beibei Zhang,Guoqiang Zhang,Qinmiao Sun,Weihong Wang,Qiang Wang,Wenxin Zhang,Dahua Chen
Craniofacial microsomia (CFM) is a congenital defect that usually results from aberrant development of embryonic pharyngeal arches. However, the molecular basis of CFM pathogenesis is largely unknown. Here, we employ the zebrafish model to investigate mechanisms of CFM pathogenesis. In early embryos, tet2 and tet3 are essential for pharyngeal cartilage development. Single-cell RNA sequencing reveals that loss of Tet2/3 impairs chondrocyte differentiation due to insufficient BMP signaling. Moreover, biochemical and genetic evidence reveals that the sequence-specific 5mC/5hmC-binding protein, Sall4, binds the promoter of bmp4 to activate bmp4 expression and control pharyngeal cartilage development. Mechanistically, Sall4 directs co-phase separation of Tet2/3 with Sall4 to form condensates that mediate 5mC oxidation on the bmp4 promoter, thereby promoting bmp4 expression and enabling sufficient BMP signaling. These findings suggest the TET-BMP-Sall4 regulatory axis is critical for pharyngeal cartilage development. Collectively, our study provides insights into understanding craniofacial development and CFM pathogenesis.
研究领域:
发育生物学
·
分子遗传学
·
颅面生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2019
·
IF 8.355
Pengfei Wei,Zuoying Yuan,Wei Jing,Yiqian Huang,Qing Cai,Binbin Guan,Zihao Liu,Xu Zhang,Jianping Mao,Dafu Chen,Xiaoping Yang
Alendronate, a nitrogen-containing bisphosphate, is commonly used for the treatment of osteoporosis, showing the potential in enhancing osteogenesis. To improve the osteo-promoting effect of injectable biomineralized microspheres for bone tissue engineering applications, in this study, alendronate was incorporated onto the microspheres during their biomineralization procedure in simulated body fluid (SBF). For the purpose, the microspheres were made of biodegradable poly( l -lactide)-poly(ethylene glycol) block copolymer, which had rough surface with gelatin coating via the (W 1 /O)/W 2 emulsion preparation method. Different amounts (25 μM, 50 μM or 100 μM) of alendronate were dissolved in the 5-times SBF and incorporated as calcium minerals depositing onto the microspheres, and thus displaying different release behaviors of alendronate. The cell culture results using bone marrow mesenchymal stromal cells (BMSCs) demonstrated that the microspheres prepared from the 50 μM of alendronate had the strongest promotion on osteogenic differentiation, while displayed insignificant adverse effect on cell proliferation and viability. By adding Noggin (an inhibitor for bone morphogenetic protein (BMP)) into the culture systems, it was proposed that BMP signaling pathway was one of the possible pathways for alendronate playing its activating effect. In vivo evaluation was conducted by injecting the alendronate-loaded microspheres subcutaneously into rabbit back, in which, histological and immunohistological analysis were done to assess ectopic neovascularization and osteogenesis. Promisingly, the potential of biomineralized microspheres in promoting osteogenesis was significantly strengthened with the incorporation of alendronate. Therefore, a proper application of alendronate in bone repairing materials can be an effective strategy targeting bone regeneration.
研究领域:
生物医学工程
·
组织工程
·
药剂学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）