Sweroside‐mediated mTORC1 hyperactivation in bone marrow mesenchymal stem cells promotes osteogenic differentiation

Ding, Yan; Jiang, Huaji; Meng, Biying; Zhu, Biao; Xiao, Yu; Xiang, Guangda

doi:10.1002/jcb.28882

Cited by 23 publications

(20 citation statements)

References 28 publications

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“…The primer sequences are listed in ESM Table 2. Western blot was performed on isolated glomeruli or cell extracts as described previously [29]. The antibodies are listed in ESM Table 1.…”

Section: Rt-pcr and Western Blotmentioning

confidence: 99%

MYDGF attenuates podocyte injury and proteinuria by activating Akt/BAD signal pathway in mice with diabetic kidney disease

Wang

et al. 2020

Diabetologia

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Aims/hypothesis Myeloid-derived growth factor (MYDGF), mainly secreted by bone marrow-derived cells, has been known to promote glucagon-like peptide-1 production and improve glucose/lipid metabolism in mouse models of diabetes, but little is known about the functions of MYDGF in diabetic kidney disease (DKD). Here, we investigated whether MYDGF can prevent the progression of DKD. Methods In vivo experiments, both loss-and gain-of-function strategies were used to evaluate the effect of MYDGF on albuminuria and pathological glomerular lesions. We used streptozotocin-treated Mydgf knockout and wild-type mice on high fat diets to induce a model of DKD. Then, albuminuria, glomerular lesions and podocyte injury were evaluated in Mydgf knockout and wild-type DKD mice treated with adeno-associated virus-mediated Mydgf gene transfer. In vitro and ex vivo experiments, the expression of slit diaphragm protein nephrin and podocyte apoptosis were evaluated in conditionally immortalised mouse podocytes and isolated glomeruli from non-diabetic wild-type mice treated with recombinant MYDGF. Results MYDGF deficiency caused more severe podocyte injury in DKD mice, including the disruption of slit diaphragm proteins (nephrin and podocin) and an increase in desmin expression and podocyte apoptosis, and subsequently caused more severe glomerular injury and increased albuminuria by 39.6% compared with those of wild-type DKD mice (p < 0.01). Inversely, MYDGF replenishment attenuated podocyte and glomerular injury in both wild-type and Mydgf knockout DKD mice and then decreased albuminuria by 36.7% in wild-type DKD mice (p < 0.01) and 34.9% in Mydgf knockout DKD mice (p < 0.01). Moreover, recombinant MYDGF preserved nephrin expression and inhibited podocyte apoptosis in vitro and ex vivo. Mechanistically, the renoprotection of MYDGF was attributed to the activation of the Akt/Bcl-2-associated death promoter (BAD) pathway. Conclusions/interpretationThe study demonstrates that MYDGF protects podocytes from injury and prevents the progression of DKD, providing a novel strategy for the treatment of DKD.

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“…The primer sequences are listed in ESM Table 2. Western blot was performed on isolated glomeruli or cell extracts as described previously [29]. The antibodies are listed in ESM Table 1.…”

Section: Rt-pcr and Western Blotmentioning

confidence: 99%

MYDGF attenuates podocyte injury and proteinuria by activating Akt/BAD signal pathway in mice with diabetic kidney disease

Wang

et al. 2020

Diabetologia

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“…Therefore, the biological functions of BMSCs are vital for the homeostasis of bone. Iron is an important nutritional element for the human body [40]. However, excess iron accumulation could bring damage to cells, tissues and even organs, leading to various types of disease [41].…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV protects against iron loading‐induced abnormal differentiation of bone marrow mesenchymal stem cells (BMSCs)

Jin

Ren

et al. 2021

FEBS Open Bio

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Iron loading has been reported to be a common stress in the development of cells, and this might be related to bone loss and osteoporosis. Astragaloside IV (ASI‐IV), a pure compound derived from Radix Astragali, has been reported to exhibit cardioprotective, anti‐inflammatory, antioxidant, antiasthmatic and anticancer effects. The aim of this study was to investigate whether ASI‐IV could reverse iron loading‐induced inhibition of cell viability, proliferation, pluripotency and osteogenesis and promote adipogenesis of bone marrow mesenchymal stem cells (BMSCs). Ferric ammonium citrate (FAC) was used to stimulate iron loading conditions. ASI‐IV was observed to ameliorate the FAC‐induced reduction of cell viability, proliferation, pluripotency and osteogenesis of BMSCs. In addition, ASI‐IV could block the increased adipogenesis of BMSCs after FAC treatment. We intraperitoneally injected mice with 250 mg·kg−1 iron dextran, with or without ASI‐IV (40 mg·kg−1), for 4 weeks. ASI‐IV inhibited the iron loading‐induced bone loss of these mice. Furthermore, ASI‐IV played a protective role in iron loading‐induced abnormal differentiation of BMSCs by regulating iron homeostasis and metabolism. In summary, our study suggesteds that ASI‐IV might have potentials for development into a novel therapeutic strategy for the treatment of iron loading‐induced abnormal differentiation of BMSCs and osteoporosis.

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“…However, samples from Sichuan province showed a higher content of swertiamarin, and pharmacological research has revealed that this characteristic compound possesses anti-diabetic and anti-hyperlipidemic effects [28], and inhibits liver fibrosis [29]. Additionally, samples from Qinghai province have shown a higher content of sweroside, which exhibited a hepatoprotective effect [30], protective effects on osteoporosis [31], and aconitine-induced cardiac toxicity effects [32]. In view of the above reasons, it remains a challenge to estimate the herb quality of different populations.…”

Section: Discussionmentioning

confidence: 99%

Traceability of Geographical Origin in Gentiana straminea by UPLC-Q Exactive Mass and Multivariate Analyses

et al. 2019

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The root of Gentiana straminea Maxim. (Gentianaceae), is officially listed as “Qin-Jiao” in the Chinese Pharmacopoeia for the treatment of rheumatic arthritis, icteric hepatitis, constipation, pain, and hypertension. To establish the geographical origin traceability in G. straminea, its chemical profiles were determined by a UPLC-Q exactive mass spectrometer, from which 43 compounds were identified by comparing retention times and mass spectrometry. Meanwhile, a pair of isomers (loganin and secologanol) was identified by mass spectrometry based on their fragmentation pathway. A total of 42 samples from difference habitats were determined by an UPLC-Q exactive mass spectrometer and the data were assayed with multivariate statistical analysis. Eight characteristic compounds were identified to determine the geographical origin of the herb. To estimate the key characteristic markers associated with pharmacological function, the inhibiting activities of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced macrophages were examined. This finding is crucial in realizing the determination of botanical origin and evaluating the quality of G. straminea.

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Sweroside‐mediated mTORC1 hyperactivation in bone marrow mesenchymal stem cells promotes osteogenic differentiation

Cited by 23 publications

References 28 publications

MYDGF attenuates podocyte injury and proteinuria by activating Akt/BAD signal pathway in mice with diabetic kidney disease

MYDGF attenuates podocyte injury and proteinuria by activating Akt/BAD signal pathway in mice with diabetic kidney disease

Astragaloside IV protects against iron loading‐induced abnormal differentiation of bone marrow mesenchymal stem cells (BMSCs)

Traceability of Geographical Origin in Gentiana straminea by UPLC-Q Exactive Mass and Multivariate Analyses

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