Astragalus polysaccharide ameliorates bone marrow haematopoietic failure in mice with aplastic anaemia via the Hippo/TERT signalling pathway.

OBJECTIVE

To study the effects of astragalus polysaccharide (APS) on aplastic anaemia (AA) in mice through modulation of the upstream and downstream effectors of the Hippo pathway. Further, we investigated the underlying mechanisms of APS in the treatment of AA to provide possible therapeutic strategies and drugs for clinical use.

METHODS

BALB/c mice were subjected to 4 Gy X-ray irradiation and subsequently injected with lymphocytes from DBA/2 donor mice by using the tail vein to establish an AA mouse model. Next BALB/c mice were randomly divided into five groups: control (untreated), AA (model), and three APS remedy groups - LA (low-dose APS, 200 mg/kg), MA (medium-dose APS, 400 mg/kg), and HA (high-dose APS, 800 mg/kg). The mice were sacrificed after 14 d of continuous gavage with different doses of APS or saline, and the bone marrow, spleen and liver were obtained. The haematopoietic condition, apoptosis levels, and the expression of Large Tumour Suppressor 1/2 (LATS 1/2), transcriptional co-activator of activation (TCA) Yes-associated protein (YesAP), transcriptional enhancer of adherence domain (TEAD) protein, and Telomerase Reverse Transcriptase (TERT), were analysed.

RESULTS

Compared with control mice, mice in the AA group exhibited a reduction in peripheral blood cell counts, a significant decrease in the haematopoietic area, increased adipocyte infiltration, and overall haematopoietic failure, mirroring the clinical presentation of AA; After 14 days of treatment with different doses of APS, the APS-treated group, in comparison to the untreated AA group, showed an increase in peripheral blood cell counts (P < 0.05), an expansionof the haematopoietic area in the bone marrow, restoration of haematopoietic function (P < 0.05), and a marked reduction in adipocyte infiltration within the bone marrow(P < 0.05). Cell infiltration into the bone marrow was also reduced. Further experiments revealed that the expression levels of TERT, LATS 1/2, YAP, and TEAD were elevated in the treated mice (P < 0.05).

CONCLUSION

X-ray irradiation combined with T-lymphocyte infusion successfully established an AA mouse model, and APS administration modulated the expression of TERT and the Hippo pathway effectors LATS 1/2, YAP, and TEAD, which are implicated in the pathogenesis of AA. This modulation resulted in the restoration of bone marrow haematopoietic function in AA mice, suggesting APS as a promising therapeutic agent for the treatment of AA.