Ask about this productRelated genes to: P4HA1 antibody
- Gene:
- P4HA1 NIH gene
- Name:
- prolyl 4-hydroxylase subunit alpha 1
- Previous symbol:
- P4HA
- Synonyms:
- C-P4Halpha(I)
- Chromosome:
- 10q22.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-02-23
- Date modifiied:
- 2016-01-27
Related products to: P4HA1 antibody
Related articles to: P4HA1 antibody
- 4-Hydroxyproline (4Hyp) is crucially important for the collagen triple helix formation and its thermal stability. It is catalyzed by collagen prolyl 4-hydroxylases (C-P4Hs) that are αβ tetramers of two identical catalytic α-subunits (encoded by P4HA1, P4HA2 and P4HA3) and two β-subunits that are protein disulfide isomerases (PDI). The functions of isoenzymes I and II (P4HA1 and P4HA2) are widely studied but very little is currently known about P4HA3. Here we show that P4ha1 is generally the most abundant isoform in mouse, whereas P4ha3 expression is tissue and developmental stage specific. P4ha3 expression is highest in the developing skeletal system and peaks at E12.5 together with the other isoforms. Postnatal P4ha3 expression is low and mainly present in calvaria, lung, heart and muscle. The P4ha3 expression virtually disappears at or after 1 week of age in all tissues studied. To evaluate the P4HA3 function in collagen synthesis, we produced cells that lack P4HA3 (P4ha3) and cells that have P4HA3 as the only isoform (P4ha1;P4ha2) by CRISPR/Cas9. C-P4H activity assays indicated no 4Hyp formation in type I collagen by the P4ha1;P4ha2 cells, suggesting that the remaining isoform P4HA3 does not participate in type I collagen synthesis. The P4ha3 cells secreted intact pepsin-resistant collagen that had similar 4Hyp content and melting temperature as WT collagen. Secreted collagen also assembled into supramolecular collagen fibrils. In conclusion, our results provide new insights into collagen biosynthesis and suggest that prolyl 4-hydroxylation of type I collagen is mediated by P4HA1 and P4HA2 but not by P4HA3. - Source: PubMed
Publication date: 2026/04/16
Karjalainen EmmaRappu PekkaIzzi ValerioMiinalainen IlkkaHeino JyrkiMyllyharju JohannaSalo Antti M - The Transmembrane protein 45 (TMEM45) family comprises multi-pass transmembrane proteins that harbor the ancient DUF716 domain and are predominantly localized to the endomembrane system (endoplasmic reticulum, Golgi apparatus). In mammals, TMEM45 members exhibit highly tissue-specific expression patterns and their functions are tightly linked to endomembrane activities. TMEM45A directly binds prolyl-4-hydroxylase (P4HA1) to modulate extracellular matrix (ECM) synthesis, thereby contributing to fibrosis and corneal disorders. TMEM45B participates in the Golgi processing and trafficking of nociceptive signaling molecules and also influences viral replication. Another paralog, TEDDM1, is implicated in sperm maturation. Expression of TMEM45 proteins is stringently regulated by upstream signaling cascades including TGF-β1/Smad, hypoxia/HIF-1α, calcium signaling, and JAK2/STAT3. In turn, these proteins serve as regulatory nodes that modulate downstream pathways such as Jagged1/Notch, Rho/ROCK, unfolded protein response (UPR), NF-κB, AKT/mTOR, Wnt/β-catenin, DNA-damage repair, and apoptosis. This review integrates current knowledge on the tissue distribution and upstream/downstream signaling networks of TMEM45 proteins to clarify endomembrane protein function and provide new perspectives on intracellular signal transduction mechanisms. - Source: PubMed
Publication date: 2026/03/25
Zhang XiaoqianZhang YanpingZhai ZhenguoWang Xietong - Keloids are characterized by excessive collagen deposition and persistent inflammation, causing high morbidity and recurrence with limited effective treatments. In this study, MIL-100(Fe)- a metal-organic framework composed of ferrous/ferric ion nodes and 1,3,5-benzenetricarboxylate ligands- is synthesized via a microwave-assisted hydrothermal method and demonstrated nanoscale particle size (141.7 nm). In vitro, human keloid fibroblasts maintained >90% viability after 48 h with MIL-100(Fe) treatment and showed robust cellular uptake within 2 h, compared to PBS-treated controls. MIL-100(Fe) significantly reduced fibroblast migration and downregulated fibrosis-associated proteins after 48 h, including collagen I, collagen III, transforming growth factor beta 1 (TGF-β1), SMAD3, and prolyl 4-hydroxylase subunit alpha 1 (P4HA1). Western blot analysis confirmed that TGF-β1 expression is more strongly suppressed in human keloid fibroblasts than in human monocytes. In an in vivo humanized keloid mouse model, four weeks of intralesional MIL-100(Fe) injection reduced fibrous tissue volume by 27% by week two post-treatment compared with controls. Histological analysis showed decreased fibroblast density, decreased collagen fiber area, polarized macrophage infiltration, and vacuolization in the MIL-100(Fe) treated group. These findings suggest that MIL-100(Fe) selectively targets the TGF-β/SMAD pathway, thereby reducing collagen deposition and fibrosis, and highlight its potential as a therapeutic nanoplatform for keloid treatment. - Source: PubMed
Publication date: 2026/04/10
Cheng Po-HsiuMatar Dany YChung Wei-TingPanayi Adriana CChen Yen-ChangYu Yu-ShengChen YunchingKuo Tzu-LeiHung Wen-ChunKao Huang-KaiWu Kevin C-W - The lack of effective therapeutic options available for microsatellite stable (MSS) colorectal cancer (CRC) remains a significant clinical challenge. Interestingly, chemotherapy-resistant cancer cells can be induced to undergo ferroptosis, prompting our investigation into RSL3, a potent ferroptosis inducer, in MSS CRC cells. Our findings revealed that while RSL3 suppressed the growth of MSS CRC cells, a subset displayed resistance. Single-cell sequencing uncovered an aberrant activation of hypoxia pathways in RSL3-resistant MSS CRC cells. Inhibiting HIF-1α, the key transcription factor driving hypoxia signaling, restored RSL3 sensitivity in these resistant cells; moreover, this sensitivity was attenuated upon HIF-1α overexpression. Chromatin immunoprecipitation assays further demonstrated that in RSL3-resistant cells, HIF-1α was enriched at the promoter of P4HA1, a gene implicated in ferroptosis resistance, thereby enhancing its expression. Additionally, in vivo experiments using syngeneic transplantation of CT26 cells in mice revealed that combining RSL3 with an HIF-1α inhibitor markedly enhanced tumor suppression and metastasis prevention, concomitant with increased intratumoral infiltration of CD8 T cells and CD86 macrophages. Notably, the combination enhanced the antitumor response of anti-PD1, a treatment otherwise ineffective on this tumor. These findings suggest that targeting HIF-1α represents a promising therapeutic strategy when used in conjunction with a ferroptosis inducer for the treatment of MSS CRC. - Source: PubMed
Publication date: 2026/04/01
Yang ZhiyingMa RuiWu WeiliShi YingChen YouLuo XiaotongLi KaiWu LiangcaiWang BoZhang BoyuYuan Ping - Diabetic cardiomyopathy (DCM) is a severe complication of end-stage diabetes characterised by cardiac hypertrophy and heart failure. Previous studies have shown that aerobic exercise enhances the body's antioxidant capacity, protects the heart, and alleviates DCM-mediated heart damage; however, the specific mechanism remains unclear. The aim of this study was to investigate the protective effects and underlying mechanisms of aerobic exercise against DCM. - Source: PubMed
Publication date: 2026/03/18
Xie SicongWang MingjunYu ChenshuoZhou FeiZheng YuZhang NingChen YushanKong WeihanSi WenzheXu JiaxuanZhang YangWang Lei