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

Autor: Suzuki Y; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan., Kawasaki T; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan., Tatsumi K; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan., Okaya T; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan., Sato S; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan., Shimada A; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan., Misawa T; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.; Synergy Institute for Futuristic Mucosal Vaccine Research and Development, Chiba University, Chiba 260-8670, Japan., Hatano R; Department of Therapy Development and Innovation for Immune disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan., Morimoto C; Department of Therapy Development and Innovation for Immune disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan., Kasuya Y; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.; Department of Pharmacology, Faculty of Pharmacy, Juntendo University, Chiba 279-0013, Japan., Hasegawa Y; Department of Applied Genomics, Kazusa DNA Research Institute, Chiba 292-0818, Japan., Ohara O; Department of Applied Genomics, Kazusa DNA Research Institute, Chiba 292-0818, Japan., Suzuki T; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.; Synergy Institute for Futuristic Mucosal Vaccine Research and Development, Chiba University, Chiba 260-8670, Japan.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Nov 23; Vol. 25 (23). Date of Electronic Publication: 2024 Nov 23.
DOI: 10.3390/ijms252312599
Abstrakt: In hypoxic pulmonary hypertension (PH), pulmonary vascular remodeling is characterized by the emergence of activated adventitial fibroblasts, leading to medial smooth muscle hyperplasia. Previous studies have suggested that CD26/dipeptidyl peptidase-4 (DPP4) plays a crucial role in the pathobiological processes in lung diseases. However, its role in pulmonary fibroblasts in hypoxic PH remains unknown. Therefore, we aimed to clarify the mechanistic role of CD26/DPP4 in lung fibroblasts in hypoxic PH. Dpp4 knockout ( Dpp4 KO) and wild-type (WT) mice were exposed to hypoxia for 4 weeks. The degree of PH severity and medial wall thickness was augmented in Dpp4 KO mice compared with that in WT mice, suggesting that CD26/DPP4 plays a suppressive role in the development of hypoxic PH. Transcriptome analysis of human lung fibroblasts cultured under hypoxic conditions revealed that TGFB2 , TGFB3 , and TGFA were all upregulated as differentially expressed genes after DPP4 knockdown with small interfering RNA treatment. These results suggest that CD26/DPP4 plays a suppressive role in TGFβ signal-regulated fibroblast activation under hypoxic conditions. Therefore, CD26/DPP4 may be a potential therapeutic target in patients with PH associated with chronic hypoxia.
Databáze: MEDLINE
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