RGD Reference Report - Monocrotaline pyrrole enhanced bone morphogenetic protein 7 signaling transduced by alternative activin A receptor type 2A in pulmonary arterial smooth muscle cells. - Rat Genome Database

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Monocrotaline pyrrole enhanced bone morphogenetic protein 7 signaling transduced by alternative activin A receptor type 2A in pulmonary arterial smooth muscle cells.

Authors: Sun, Na  Chen, Yiqiang  Yu, Fangli  Zhixin, Fan  Lin, Jianhui  Sun, Binfeng  Yu, Bo  Cheng, Xiaohan  Zheng, Xiaodong  Wu, Bingxiang 
Citation: Sun N, etal., Eur J Pharmacol. 2019 Nov 15;863:172679. doi: 10.1016/j.ejphar.2019.172679. Epub 2019 Sep 19.
RGD ID: 155888480
Pubmed: PMID:31542483   (View Abstract at PubMed)
DOI: DOI:10.1016/j.ejphar.2019.172679   (Journal Full-text)


BACKGROUND: Increased expression levels of bone morphogenetic protein 7 (BMP7) are associated with poor prognosis in pulmonary hypertension patients. However, whether BMP7 signaling conspire to involve in the proliferation of pulmonary artery smooth muscle cells (PASMC) underlying monocrotaline (MCT) induced pulmonary arterial hypertension (PAH) remain unclear.
METHODS AND RESULTS: Western blot experiments found BMP7 was increased in pulmonary arteries isolated from MCT-PAH rat. In addition, monocrotaline pyrrole (MCTP), the putative toxic metabolite of the MCT, increases the expression of BMP7, proliferating cell nuclear antigen (PCNA) and activin A receptor type 2A, but decreases bone morphogenetic protein receptor type 2 in cultured pulmonary artery smooth muscle cells (PASMC). In PASMCs, exogenous BMP7 leads to the decreasing expression of activin A receptor type 2, increasing phosphorylation of p38MAPK and elevation of P21. However, BMP7 treatment results in the increasing expression of activin A receptor type 2A, p38MAPK, and PCNA in bone morphogenetic protein receptor type 2 knockdown PASMCs. Knockdown of activin A receptor type 2A abrogated the MCTP-induced PCNA and cell cycle progression.
CONCLUSIONS: MCTP treatment lead to the expression of BMP7, suppression of bone morphogenetic protein receptor type 2 but increasing expression of activin A receptor type 2A, the BMP7 mediated PASMC proliferation via preferential activation of an activin A receptor type 2A signaling axis.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BMP7HumanPulmonary Arterial Hypertension  ISOBmp7 (Rattus norvegicus)protein:increased expression:lung and pulmonary artery (rat)RGD 
Bmp7RatPulmonary Arterial Hypertension  IEP protein:increased expression:lung and pulmonary artery (rat)RGD 
Bmp7MousePulmonary Arterial Hypertension  ISOBmp7 (Rattus norvegicus)protein:increased expression:lung and pulmonary artery (rat)RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BMP7Humanmonocrotaline increases expression ISOBmp7 (Rattus norvegicus)monocrotaline increases expression of Bmp7 protein in rat lung and pulmonary arteryRGD 
Bmp7Ratmonocrotaline increases expression EXP monocrotaline increases expression of Bmp7 protein in rat lung and pulmonary arteryRGD 
Bmp7Mousemonocrotaline increases expression ISOBmp7 (Rattus norvegicus)monocrotaline increases expression of Bmp7 protein in rat lung and pulmonary arteryRGD 

Objects Annotated

Genes (Rattus norvegicus)
Bmp7  (bone morphogenetic protein 7)

Genes (Mus musculus)
Bmp7  (bone morphogenetic protein 7)

Genes (Homo sapiens)
BMP7  (bone morphogenetic protein 7)


Additional Information