Transcriptome Analysis of Fibroblasts in Hypoxia-Induced Vascular Remodeling: Functional Roles of CD26/DPP4

Area of Science:

• Pulmonary Hypertension Research
• Fibroblast Biology
• Molecular Medicine

Background:

• Hypoxic pulmonary hypertension involves adventitial fibroblast activation and smooth muscle hyperplasia.
• CD26/dipeptidyl peptidase-4 (DPP4) is implicated in lung disease pathobiology.
• The role of DPP4 in pulmonary fibroblasts during hypoxic PH is not well understood.

Purpose of the Study:

• To elucidate the mechanistic role of CD26/DPP4 in lung fibroblasts within hypoxic pulmonary hypertension.
• To investigate the suppressive potential of CD26/DPP4 in the context of hypoxic PH.

Main Methods:

• Utilized Dpp4 knockout (Dpp4 KO) and wild-type (WT) mice exposed to hypoxia for 4 weeks.
• Performed transcriptome analysis on human lung fibroblasts with Dpp4 knockdown via small interfering RNA under hypoxic conditions.

Main Results:

• Dpp4 KO mice exhibited augmented PH severity and medial wall thickness compared to WT mice.
• Upregulation of TGFB2, TGFB3, and TGFA was observed in Dpp4-knockdown human lung fibroblasts under hypoxia.
• CD26/DPP4 demonstrated a suppressive role in TGFβ signal-regulated fibroblast activation.

Conclusions:

• CD26/DPP4 plays a suppressive role in the development of hypoxic pulmonary hypertension.
• CD26/DPP4 modulates fibroblast activation pathways, particularly TGFβ signaling, under hypoxic conditions.
• CD26/DPP4 represents a potential therapeutic target for pulmonary hypertension associated with chronic hypoxia.