PTBP1 Targets ILK to Regulate the Hypoxia-Induced Phenotypic Transformation of Pulmonary Artery Smooth Muscle Cells

Abstract

Purpose

Pulmonary hypertension (PH) is a pathological process mainly characterized by the progressive increase in pulmonary vascular resistance. The degradation of pulmonary artery smooth muscle cells (PASMCs) from contractile/differentiated phenotype to synthetic/dedifferentiated phenotype is a key factor for hypoxic pulmonary hypertension.

Materials and Methods

In this study, qPCR was performed to evaluate the gene expression of mRNAs. Western blot, immunofluorescence and RNA pull down were used to detect gene expression levels.

Results

We found that the gene expression of polypyrimidine tract-binding protein1 (PTBP1) was increased significantly in a time-dependent manner in rats PA tissues and PASMCs after hypoxia. PTBP1 knockdown can inhibit the phenotypic transition of PASMCs. PTBP1 inhibits the phenotypic transition of PASMCs. In addition, PTBP1 inhibits the integrin-linked kinase (ILK) expression under hypoxic conditions, thereby down-regulating the expression of downstream proteins. It inhibits the phenotypic transition of PASMCs and alleviates pulmonary hypertension.

Conclusion

In conclusion, PTBP1/ILK axis promotes the development of PH via inducing phenotypic transition of PASMCs. This may provide a novel therapy for PH.

Keywords:

• pulmonary hypertension
• polypyrimidine tract-binding protein 1
• integrin-linked kinase
• pulmonary artery smooth muscle cells

Acknowledgment

This study is supported by National Natural Science Foundation of China (Research Grant no. 81600227).

Author Contributions

All authors made substantial contributions to the design and conception of the study, and acquisition, analysis and interpretation of data, and took part in either drafting or revising the manuscript. All authors gave final approval of the version to be published, have agreed on the journal to which the article has been submitted, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Disclosure

There is no interest conflict of all the authors.