Ask about this productRelated genes to: PPIF antibody
- Gene:
- PPIF NIH gene
- Name:
- peptidylprolyl isomerase F
- Previous symbol:
- -
- Synonyms:
- hCyP3, Cyp-D
- Chromosome:
- 10q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-06-02
- Date modifiied:
- 2015-09-07
Related products to: PPIF antibody
Related articles to: PPIF antibody
- Diabetic foot ulcers (DFU) are a major complication of diabetes, and its pathogenesis remains incompletely elucidated. Converging evidence indicates that oxidative stress and dysregulated mitochondrial polarization participate in DFU progression, nominating these processes as therapeutically actionable targets. This study integrates bulk and single-cell transcriptomic data with machine learning to reconstruct cross-scale, cell type-resolved molecular atlases and regulatory networks. Macrophages and fibroblasts emerged as communication hubs, dominating pathway enrichment and ligand-receptor programs such as macrophage migration inhibitory factor signaling pathway (MIF), ANNEXIN signaling pathway, and COMPLEMENT signaling pathway. Peptidylprolyl isomerase F (PPIF), which encodes cyclophilin D (CypD) and apolipoprotein E (APOE) were further prioritized as putative drivers within macrophages and fibroblasts, and a five-gene classifier was derived with robust performance (internal/external AUC = 0.833/0.933). Within DFU lesions, under the control of non-coding RNA circuitry, SOX5 may shape the inflammatory microenvironment, APOE may participate in lipid-metabolic remodeling, and PPIF (CypD) likely links reactive oxygen species (ROS) accumulation to a p53-dependent mitochondrial death pathway (necroptosis/apoptosis). Orthogonal validation showed significantly increased CypD in diabetic foot ulcer skin (DFUS) and diabetic foot ulcer tendon (DFUT) relative to diabetic foot skin (DFS) and DFT (Diabetic foot tendon), with up-regulated p53 and Cytc and down-regulated ApoE in DFUS; in primary foot-skin fibroblasts, a high-glucose plus tert-butyl hydroperoxide (HG+TBHP) model reproduced elevated ROS, loss of mitochondrial Δψm (mitochondrial membrane potential), growth restriction, and apoptosis, supporting a ROS-CypD/mPTP (mitochondrial permeability transition pore)-Δψm depolarization-p53/Cytc apoptosis axis. The delineated PPIF-centered regulatory network includes upstream transcription factors CEBPB/REL/SPI1 and a downstream ceRNA axis comprising miR-128-3p/miR-23a-3p-long non-coding RNA OIP5-AS1. Additionally, the significant role of polarization-specific reprogramming in regulating macrophage function highlights therapeutic strategies focused on metabolic reprogramming and inhibition of the PPIF/mPTP pathway. Collectively, a cell type-resolved molecular map of DFU is provided, healing-relevant cell populations and regulatory circuits are prioritized, and a translational, testable intervention framework is proposed. - Source: PubMed
Publication date: 2026/04/01
Guo ZeaoZeng ZhaoyangMa XuepengJing Shuai-ShuaiWu YuShan BinPan HaibangShi YuhongLiu AiJiang HugangLi Ning - is the primary etiological agent of community-acquired pneumonia (CAP). Pneumococci promote severe lung injury through the release of virulence factors, including pneumolysin (PLY). Obesity/diabetes increases pneumonia-associated mortality, but the mechanisms remain elusive. We found that obese db/db mice have increased pulmonary barrier disruption to PLY. Previously we showed that upregulation of NOX1 in endothelial cells (EC) of db/db mice drives endothelial dysfunction, but a role for NOX1 in PLY-induced lung injury, especially in diabetic conditions, has not yet been described. Increased NOX1 in lung ECs dose-dependently increased superoxide and EC barrier disruption ( < 0.05). Even at low activity levels, NOX1 greatly potentiated PLY-induced EC barrier disruption, whereas loss of NOX1 activity, either pharmacological or genetic, reduced barrier disruption ( < 0.05). Blockade of calcium entry protected the EC barrier from combined PLY and NOX1, indicating a key role for calcium. Hyperglycemia amplified PLY-enduced EC barrier disruption and intracellular calcium and these effects were mitigated by NOX1 inhibition and silencing ( < 0.05). NOX1-enhanced calcium entry was reduced by knockout of calcium sensor STIM1, and PLY-induced barrier disruption was reduced by STIM1 inhibition. Levels of STIM1, Orai1, TRPV4, or TRPC4 were unchanged by HG, but TRPC1 significantly increased ( < 0.05). NOX1 and HG promoted increased STIM1 and TRPC1 binding, and silencing TRPC1 ameliorated PLY-induced barrier disruption ( < 0.05). Increased calcium promoted mitochondrial permeability transition pore (MPTP) opening and PPIF inhibition protected EC barrier function ( < 0.05). These results suggest that elevated glucose levels in obesity primes EC barrier disruption by amplifying PLY-induced calcium influx via a novel NOX1, STIM1, TRPC1 and MPTP signaling axis. - Source: PubMed
Publication date: 2026/02/24
Haigh StephenChen FengYu YanfangBordan ZsuzsannaLi XueyiSridhar SupriyaRomero Maritza JChakraborty TrinadCsanyi GaborJoshua Austin TPatel Tej VBrown Zachary LShivers Mitchel ASellers Hunter GAnanna FarhanaFukai TohruUshio-Fukai MasukoBelin de Chantemele Eric JVerin AlexanderStepp David WLucas RudolfFulton David J R - Currently, no therapies are approved for alcohol-associated liver disease (ALD). Here, we identify cyclophilin D (CypD) as a critical mediator in the progression of ALD. We observe elevated expression of CypD in ALD patients and a corresponding mouse model. Hepatocyte-specific knockout of CypD mitigates hepatic mitochondrial dysfunction, steatosis, inflammation, and oxidative stress. Conversely, overexpression of CypD exacerbates hepatic mitochondrial stress. In vivo and in vitro experiments demonstrate that a CypD inhibitor, RN-0001, effectively and safely alleviates hepatic damage induced by ethanol exposure; these protective effects are absent in CypD-deficient mice. Biophysical assays indicate that RN-0001 directly binds to CypD. Additionally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) tests and first-in-human phase I clinical trial identify RN-0001 as a promising translational candidate for ALD therapy. Collectively, our study highlights the pathological role of CypD in ALD and introduces a preclinical candidate for its management. This study was registered at chictr.org.cn (ChiCTR2500106709). - Source: PubMed
Che ZhaoyiLuo ZhihuiXiao DongMa FashuZhou HaoxiongSong YaliGuo ShanshanYuan YuanWang HaoMak Ching-PongSo Kwok-FaiXiao Jia - Ischemia induces oxidative stress and mitochondrial dysfunction in microglia, contributing to neuro-inflammation and neuronal damage. Five furanoditerpenes -, isolated from the marine sponge , have previously shown neuroprotective effects related to their capacity to bind cyclophilin D (CypD), a protein involved in ischemia. In this study, the ability of compounds - to alleviate ischemic damage was evaluated on BV2 microglial cells. First, cells were incubated under oxygen deprivation for 6 h, and the five compounds were able to improve cell viability at micromolar concentrations (0.001-1 μM). Then, hypoxia was combined with the inflammatory stimulus lipopolysaccharide and with glucose deprivation, and metabolites maintained their protective effects. When oxygen and glucose deprivation was followed by 6 h of reperfusion, compounds - also mitigated the damage produced on microglia. Moreover, these furanoditerpenes reduced reactive oxygen species overproduction and restored mitochondrial membrane potential, key factors in ischemic damage. This effect was mediated by the regulation of CypD since compounds , , and reduced its expression under ischemia conditions. Finally, -well coculture experiments were performed between microglial and SH-SY5Y neuronal cells. In this assay, compounds , , and protected neuronal cells from microglial-induced neurotoxicity under ischemia/reperfusion conditions. These findings suggest that metabolites display mitochondrial-mediated antioxidant and cytoprotective effects under ischemic conditions through CypD modulation. Given the limitations of current Cyps inhibitors like cyclosporin A, compounds - are promising therapeutic candidates for ischemia-related diseases, such as stroke. - Source: PubMed
Publication date: 2026/03/11
Castedo NoeliaAlfonso AmparoAlvariño RebecaPech-Puch DawrinAgeitos LucíaRodríguez JaimeVieytes Mercedes RJiménez CarlosBotana Luis M - While acupuncture is an established intervention for insomnia, the neurobiological mechanisms linking its modulation of brain activity to molecular-level changes remain poorly understood. This study addresses a critical gap by integrating multimodal data to uncover how electroacupuncture regulates oscillatory activity in specific brain regions and correlates these changes with proteomic alterations. - Source: PubMed
Publication date: 2026/03/04
Lin LiyuZhao YananYang YueQin ShanWang XiaoqiuWang TingLiu ChengyongWu Wenzhong