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in: JCI | Pub Med | Google Scholar Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA. Chan, Brigham and Women’s Hospital, New Research Building, Room 630N, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. In this study, we developed a more sophisticated computational method to search for overlap of functional pathways embedded in the architecture of the molecular network of PH. in: JCI | Pub Med | Google Scholar Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA. Chan, Brigham and Women’s Hospital, New Research Building, Room 630N, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. Previously, we designed a network-based bioinformatics approach () to predict in silico mi RNAs controlling PH pathogenesis — via ranking of mi RNAs by putative ability to recognize multiple targets in the same functional network of downstream PH-relevant effector genes (the “PH network,” as derived by literature curation and mapped using consolidated databases of molecular interactions). in: JCI | Pub Med | Google Scholar Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA. Chan, Brigham and Women’s Hospital, New Research Building, Room 630N, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. Micro RNAs (mi RNAs) may coordinately regulate PH progression, but the integrative functions of mi RNAs in this process have been challenging to define with conventional approaches. in: JCI | Pub Med | Google Scholar Development of the vascular disease pulmonary hypertension (PH) involves disparate molecular pathways that span multiple cell types.

The mi R-130/301 family was ranked the highest by a mi RNA spanning score, reflecting the most robust systems-level control over the expanded PH network as a whole.

Direct targets of the mi R-130/301 family (28 enlarged nodes) span all 8 gene clusters and 13 functional pathways.

(B) The mi R-130/301 family members share the same seed sequence (in red).

in: JCI | Pub Med | Google Scholar Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA. Chan, Brigham and Women’s Hospital, New Research Building, Room 630N, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. In endothelial cells, mi R-130/301 modulated apelin-mi R-424/503-FGF2 signaling, while in smooth muscle cells, mi R-130/301 modulated STAT3-mi R-204 signaling to promote PH-associated phenotypes.

in: JCI | Pub Med | Google Scholar Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA. Chan, Brigham and Women’s Hospital, New Research Building, Room 630N, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. Evaluation of pulmonary arterial endothelial cells and smooth muscle cells revealed that mi R-130/301 targeted PPARγ with distinct consequences.

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