PAC1R agonist maxadilan enhances hADSC viability and neural differentiation potential

Abstract

Pituitary adenylate cyclase‐activating polypeptide (PACAP) is a structurally endogenous peptide with many biological roles. However, little is known about its presence or effects in human adipose‐derived stem cells (hADSCs). In this study, the expression of PACAP type I receptor (PAC1R) was first confirmed in hADSCs. Maxadilan, a specific agonist of PAC1R, could increase hADSC proliferation as determined by Cell Counting Kit‐8 and cell cycle analysis and promote migration as shown in wound‐healing assays. Maxadilan also showed anti‐apoptotic activity in hADSCs against serum withdrawal‐induced apoptosis based on Annexin V/propidium iodide analysis and mitochondrial membrane potential assays. The anti‐apoptotic effects of maxadilan correlated with the down‐regulation of Cleaved Caspase 3 and Caspase 9 as well as up‐regulation of Bcl‐2. The chemical neural differentiation potential could be enhanced by maxadilan as indicated through quantitative PCR, Western blot and cell morphology analysis. Moreover, cytokine neural redifferentiation of hADSCs treated with maxadilan acquired stronger neuron‐like functions with higher voltage‐dependent tetrodotoxin‐sensitive sodium currents, higher outward potassium currents and partial electrical impulses as determined using whole‐cell patch clamp recordings. Maxadilan up‐regulated the Wnt/β‐catenin signalling pathway associated with dimer‐dependent activity of PAC1R, promoting cell viability that was inhibited by XAV939, and it also activated the protein kinase A (PKA) signalling pathway associated with ligand‐dependent activity of PAC1R, enhancing cell viability and neural differentiation potential that was inhibited by H‐89. In summary, these results demonstrated that PAC1R is present in hADSCs, and maxadilan could enhance hADSC viability and neural differentiation potential in neural differentiation medium.

Induced pluripotent stem cell‐derived conditional medium promotes Leydig cell anti‐apoptosis and proliferation via autophagy and Wnt/β‐catenin pathway

“…Furthermore, those proteins could also be up‐regulated by LiCl (20 mmol/L) added into DMEM‐LG, which is a widely used in the activation of Wnt/β‐catenin signalling . However, those proteins were again down‐regulated in iPS‐CM by XAV939 (XAV, 10 μmol/L) (Figure D,E), an inhibitor of the Wnt/β‐catenin signalling pathway . These results indicated that iPS‐CM might be mainly relied on inherent bFGF to promote the proliferation of ILCs through Wnt/β‐catenin signalling pathway.…”

“…39,40 However, those proteins were again down-regulated in iPS-CM by XAV939 (XAV, 10 lmol/L) ( Figure 6D,E), an inhibitor of the Wnt/b-catenin signalling pathway. 41 These results indicated that iPS-CM might be mainly relied on inherent bFGF to promote the proliferation of ILCs through Wnt/ b-catenin signalling pathway. And the diagram of the mechanisms underlying the promotion anti-apoptosis and proliferation of ILCs by iPS-CM is shown in Figure 6F.…”

Lack of Pituitary Adenylate Cyclase–Activating Polypeptide (PACAP) Disturbs Callus Formation

“…Lack of PACAP also influences behavior of these animals (Farkas et al 2017), and results in alterations of neuronal development (Rivnyak et al 2018). Not only the absence of the neuropeptide but its addition also affects the differentiation of chondrocytes (Juhasz et al 2014a), neurons (Guo et al 2016), and mammary epithelial cells (Csanaky et al 2014). We have demonstrated earlier that PACAP increases Ca 2+ release in osteoblasts and induces their differentiation (Juhasz et al 2014b).…”

Genome-Wide Analysis Identified a Number of Dysregulated Long Noncoding RNA (lncRNA) in Human Pancreatic Ductal Adenocarcinoma

“… 49 ANKRD30BP2 , which encoded ankyrin repeat domain 30B pseudogene 2 or CTSP-1, was expressed in 58% of prostate tumors and was capable of eliciting a humoral immune response in about 20% of patients with prostate cancer. 50 The strong expression of CYP2S1 , a cytochromes P450 family member, was associated with poor prognosis of colorectal cancer. 51 Moreover, SH3PXD2A-AS1-correlated lncRNAs, including lnc-RP11-204N11.1.1-3:9, DLX2-AS1, and lnc00458, were also significantly dysregulated (Supplemental Table 1) in the microarray analysis.…”