Calcium‐sensing receptor regulates the angiogenic differentiation of LPS‐treated human dental pulp cells via the phosphoinositide 3‐kinase/Akt pathway in vitro

Article

Author: Liu, Peiqi ; Zhang, Yuejiao ; An, Shaofeng ; Qiu, Zixin ; Yang, Ting

AbstractAimThe purpose of this study was to investigate the role of calcium‐sensing receptor (CaSR) in the angiogenic differentiation of lipopolysaccharide (LPS)‐treated human dental pulp cells (hDPCs).MethodologyThe LPS‐induced hDPCs were cultured in the medium with different combinations of CaSR agonist R568 and antagonist Calhex231. The cell proliferation, migration, and angiogenic capacity were measured by Cell Counting Kit‐8 (CCK‐8), scratch wound healing, and tube formation assays, respectively. Enzyme‐linked immunosorbent assay (ELISA), quantitative real‐time polymerase chain reaction (qRT‐PCR), and western blot were conducted to determine the gene/protein expression of CaSR, inflammatory mediators, and angiogenic‐associated markers. The activation of phosphoinositide 3‐kinase (PI3K) and protein kinase B (Akt) was assessed by western blot analysis.ResultsThe cell proliferation was elevated in response to R568 or Calhex231 exposure, but an enhanced cell migration was only found in cultures supplemented with Calhex231. Furthermore, R568 was found to potentiate the formation of vessel‐like structure, up‐regulated the protein expression of tumour necrosis factor (TNF)‐α, vascular endothelial growth factor (VEGF), and stromal cell‐derived factor (SDF)‐1; comparable influences were also observed in R568‐stimulated cells in the presence of PI3K inhibitor LY294002. In contrast, Calhex231 obviously inhibited the tube formation and VEGF protein level, whereas promoted the production of IL‐6, TNF‐α, and eNOS; however, in the presence of LY294002, Calhex231 showed a significant promotion on the protein expression of CaSR, VEGF, and SDF‐1. In addition, R568 exhibited a promotive action on the Akt phosphorylation, which can be reversed by LY294002.ConclusionsOur results demonstrated that CaSR can regulate the angiogenic differentiation of LPS‐treated hDPCs with an involvement of the PI3K/Akt signalling pathway.

17 Jun 2024·ChemBioChem

Co‐Immobilization of ADH and GDH on Metal–Organic‐Framework: An Effective Biocatalyst for Asymmetric Reduction of Ketones

Article

Author: Yang, Zhenyan ; Lin, Yu ; Su, Guorong ; Teng, Huailong ; Ran, Lu

AbstractChiral alcohols are not only important building blocks of various bioactive natural compounds and pharmaceuticals, but can serve as synthetic precursors for other valuable organic chemicals, thus the synthesis of these products is of great importance. Bio‐catalysis represents one effective way to obtain these molecules, however, the weak stability and high cost of enzymes often hinder its broad application. In this work, we designed a biological nanoreactor by embedding alcohol dehydrogenase (ADH) and glucose dehydrogenase (GDH) in metal‐organic‐framework ZIF‐8. The biocatalyst ADH&GDH@ZIF‐8 could be applied to the asymmetric reduction of a series of ketones to give chiral alcohols in high yields (up to 99 %) and with excellent enantioselectivities (>99 %). In addition, the heterogeneous biocatalyst could be recycled and reused at least four times with slight activity decline. Moreover, E. coli containing ADH and GDH was immobilized by ZIF‐8 to form biocatalyst E. coli@ZIF‐8, which also exhibits good catalytic behaviours. Finally, the chiral alcohols are further converted to marketed drugs (R)‐Fendiline, (S)‐Rivastigmine and NPS R‐568 respectively.

03 Apr 2023·Animal BiotechnologyQ4 · AGRICULTURAL & FORESTRY SCIENCE

Effect of calcium-sensing receptor on the migration and proliferation of porcine intestinal epithelial cells

Q4 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Zheng, Jie ; Wang, Jing ; Jia, Gang ; Liu, Guangmang ; Wu, Caimei ; Zhao, Hua ; Chen, Xiaoling

The rapid healing of impaired intestinal surface plays a role in maintaining intestinal homeostasis. This study investigated the effect of calcium-sensing receptor (CaSR) on the migration and proliferation of intestinal porcine epithelial cells (IPEC-J2). Results showed that cell migration area and width were increased by R568 (CaSR activator) and decreased by NPS2143 (CaSR inhibitor). The protein level of GTP-rac1 and the phosphorylation of phospholipase C gamma 1 (PLCγ1) were increased by 2 µM R568. Furthermore, R568 + 120 µM NSC23766 (Rac1 inhibitor) and R568 + 1 µM U73122 (PLCγ1 inhibitor) decreased the protein level of GTP-rac1 and the phosphorylated PLCγ1, respectively, and both inhibited cell migration compared with R568. In addition, spermine increased the protein expression levels of CaSR and the levels of GTP-rac1 and the phosphorylated PLCγ1 and thereby promoted the migration of IPEC-J2 cells. Moreover, R568 improved the proliferation of the IPEC-J2 cells. Spermine increased cell proliferation, but NPS2143 incubated with spermine decreased cell proliferation compared with the spermine group. This study suggests that CaSR activation increased cell migration by activating Rac1 and PLCγ1 signaling and improved cell proliferation, and both effects were regulated by spermine by activating CaSR.

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Indication	Highest Phase	Country/Location	Organization	Date
Hyperparathyroidism	Phase 2	-	Shire Pharmaceuticals Services Ltd.	-
Hyperparathyroidism	Phase 2	US	NPS Pharmaceuticals, Inc.	-
Hyperparathyroidism	Phase 2	JP	Kirin Holdings Co., Ltd.	-
Hyperparathyroidism	Phase 2	-	Kirin	-
Osteoporosis, Postmenopausal	Phase 2	-	Kirin	-
Osteoporosis, Postmenopausal	Phase 2	-	Amgen, Inc.	-
Osteoporosis, Postmenopausal	Phase 2	-	Shire Pharmaceuticals Services Ltd.	-
Rheumatoid Arthritis	Phase 2	-	Shire Pharmaceuticals Services Ltd.	-
Rheumatoid Arthritis	Phase 2	-	Amgen, Inc.	-
Rheumatoid Arthritis	Phase 2	-	Kirin	-

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