Transcriptional regulation of cyclophilin D by BMP/Smad signaling and its role in osteogenic differentiation.

Autor:	Sautchuk R; Center for Musculoskeletal Research, University of Rochester, Rochester, United States., Kalicharan BH; Center for Musculoskeletal Research, University of Rochester, Rochester, United States., Escalera-Rivera K; Center for Musculoskeletal Research, University of Rochester, Rochester, United States., Jonason JH; Center for Musculoskeletal Research, University of Rochester, Rochester, United States.; Department of Pathology, University of Rochester, Rochester, United States., Porter GA; Department of Pediatrics, Division of Cardiology, University of Rochester, Rochester, United States., Awad HA; Center for Musculoskeletal Research, University of Rochester, Rochester, United States.; Department of Biomedical Engineering, University of Rochester, Rochester, United States., Eliseev RA; Center for Musculoskeletal Research, University of Rochester, Rochester, United States.; Department of Pathology, University of Rochester, Rochester, United States.; Department of Pharmacology & Physiology, University of Rochester, Rochester, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2022 May 30; Vol. 11. Date of Electronic Publication: 2022 May 30.
DOI:	10.7554/eLife.75023
Abstrakt:	Cyclophilin D (CypD) promotes opening of the mitochondrial permeability transition pore (MPTP) which plays a key role in both cell physiology and pathology. It is, therefore, beneficial for cells to tightly regulate CypD and MPTP but little is known about such regulation. We have reported before that CypD is downregulated and MPTP deactivated during differentiation in various tissues. Herein, we identify BMP/Smad signaling, a major driver of differentiation, as a transcriptional regulator of the CypD gene, Ppif . Using osteogenic induction of mesenchymal lineage cells as a BMP/Smad activation-dependent differentiation model, we show that CypD is in fact transcriptionally repressed during this process. The importance of such CypD downregulation is evidenced by the negative effect of CypD 'rescue' via gain-of-function on osteogenesis both in vitro and in a mouse model. In sum, we characterized BMP/Smad signaling as a regulator of CypD expression and elucidated the role of CypD downregulation during cell differentiation. Competing Interests: RS, BK, KE, JJ, GP, HA, RE No competing interests declared (© 2022, Sautchuk et al.)
Databáze:	MEDLINE
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