Function of Adipose-Derived Mesenchymal Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension through miR-191 via Regulation of BMPR2

الملخص EN

Pulmonary arterial hypertension (PAH) is a serious condition.

However, prevailing therapeutic strategies are not effective enough to treat PAH.

Therefore, finding an effective therapy is clearly warranted.

Adipose-derived mesenchymal stem cells (ASCs) and ASCs-derived exosomes (ASCs-Exos) exert protective effects in PAH, but the underlying mechanism remains unclear.

Using a coculture of ASCs and monocrotaline pyrrole (MCTP)-treated human pulmonary artery endothelial cells (HPAECs), we demonstrated that ASCs increased cell proliferation in MCTP-treated HPAECs.

Results showed that ASCs-Exos improved proliferation of both control HPAECs and MCTP-treated HPAECs.

In addition, by transfecting ASCs with antagomir we observed that low exosomal miR-191 expression inhibited HPAECs proliferation whereas the agomir improved.

Similar results were observed in vivo using a monocrotaline (MCT)-induced PAH rat model following ASCs transplantation.

And ASCs transplantation attenuated MCT-induced PAH albeit less than the antagomir treated group.

Finally, we found that miR-191 repressed the expression of bone morphogenetic protein receptor 2 (BMPR2) in HPAECs and PAH rats.

Thus, we conjectured that miR-191, in ASCs and ASCs-Exos, plays an important role in PAH via regulation of BMPR2.

These findings are expected to contribute to promising therapeutic strategies for treating PAH in the future.