Evidence map›Paper›PMID 39022361›Full record

ArticleACS pharmacology & translational science2024

Bone Morphogenetic Protein Signaling Agonist SB4 (BMPSB4) Inhibits Corticotroph Pituitary Neuroendocrine Tumors by Activation of Autophagy via a BMP4/SMADs-Dependent Pathway.

Longyu Xu, Ruonan Ning, Xueqing Du, Yuxin Zhang, Changwei Gu, Baofeng Wang, Liuguan Bian, Qingfang Sun, Yuhao Sun, Jie Ren

Abstract read
In one paragraph

Article in ACS pharmacology & translational science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Longyu XuDepartment of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P. R. China.
Ruonan NingDepartment of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China.
Xueqing DuDepartment of Respiratory and Critical Care Medicine of Ruijin Hospital, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China.
Yuxin ZhangDepartment of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China.
Changwei GuDepartment of Neurosurgery, Ruijin Hospital, Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, P. R. China.
Baofeng WangDepartment of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P. R. China.
Liuguan BianDepartment of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P. R. China.
Qingfang SunDepartment of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P. R. China.
Yuhao SunDepartment of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P. R. China.
Jie RenDepartment of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P. R. China.ORCID https://orcid.org/0009-0005-1715-983X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Corticotroph pituitary neuroendocrine tumors (PitNETs), associated with Cushing's disease (CD), have limited treatment options other than surgical resection. Bone morphogenetic protein 4 (BMP4), a potential therapeutic target, is decreased in patients with CD. Previous studies have identified BMPSB4 as a potent agonist of the BMP4 signaling pathway. Here, we investigated the effect of BMPSB4 on the corticotroph PitNET cell line AtT20/D16v-F2 and explored the underlying mechanisms and therapeutic potential. We verified the low expression patterns of BMP4 and downstream p-SMAD1/5/9 in CD samples at the transcriptional and protein levels. In addition, BMPSB4 activated SMAD1/5/9 in a time- and concentration-dependent manner, with concomitant inhibitory effects on AtT20/D16v-F2 cells. Further RNA sequencing, transmission electron microscopy (TEM), and transfection with the mRFP-EGFP-LC3 adenoviral vector revealed that BMPSB4 induced cellular autophagy, which was the basis for the inhibitory effect of BMPSB4. Moreover, we demonstrated that autophagy induced by BMPSB4 was achieved through the SMADs-dependent pathway. In vivo, BMPSB4 inhibited tumor growth and significantly reduced adrenocorticotrophin (ACTH) and corticosterone (CORT) secretion, thereby alleviating the CD phenotype. In conclusion, this study identified BMPSB4 as an effective therapeutic agent for CD. BMPSB4 activates autophagy through a SMADs-dependent pathway, which in turn promotes autophagy-mediated cell death. Our work further elucidates the mechanism of the BMP4 signaling pathway in CD and suggests broad prospects for the development and application of BMPSB4 in CD therapy.

Identifiers

PMID39022361
PMCPMC11249644

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.