Affinage

ADM

Pro-adrenomedullin · UniProt P35318

Length
185 aa
Mass
20.4 kDa
Annotated
2026-06-09
100 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Adrenomedullin (ADM) is a secreted multifunctional peptide that signals through CGRP(8-37)- and ADM(22-52)-sensitive receptors to regulate vascular tone, endocrine secretion, and cell survival across multiple tissues (PMID:9877221, PMID:12529288). In the vasculature, ADM produces vasodilation through two parallel mechanisms in a single vessel: an endothelial receptor coupled to the nitric oxide–guanylyl cyclase axis and a smooth-muscle CGRP receptor coupled to cAMP/PKA, with responses blocked by CGRP(8-37) (PMID:12529288); ADM also drives LPS-induced hypotension in vivo through ADM(22-52)-sensitive rather than CGRP1 receptors (PMID:11210719). The ADM gene locus additionally encodes peptides with divergent vascular activity, including the vasodilatory prodepin (proADM22-41) and the vasoconstrictor adrenotensin (proADM153-185) (PMID:8196484, PMID:7637545). In the human adrenal zona glomerulosa, ADM and its receptors (L1-R and CRLR/RAMP) form an autocrine/paracrine system in which ADM inhibits angiotensin-II- and K+-stimulated aldosterone secretion while promoting proliferation and suppressing apoptosis, with the antimineralocorticoid effect requiring both the C-terminal sequence (for binding) and the six-membered ring (for activation) (PMID:9877221, PMID:11786920). ADM functions broadly as a cytoprotective and pro-survival factor: it protects Leydig cells from LPS-induced inflammation and apoptosis via PI3K/Akt signaling (PMID:27212810), modulates glioma chemosensitivity through Akt/Erk1/2 and Bax/Bcl-2 pathways under control of miR-1297 (PMID:36183123), and inhibits stem-cell senescence by suppressing the miR-152/CCNA2 axis (PMID:36310381). ADM expression is induced under hypoxia in an HIF-1α-dependent manner and enhances trophoblast invasion (PMID:32997116).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 Medium

    Established that the ADM gene locus produces bioactive peptides beyond adrenomedullin itself, showing the prodepin fragment is a vasoactive product in its own right.

    Evidence In vivo hemodynamic measurement after i.v. injection of proADM22-41 across multiple anesthetized species

    PMID:8196484

    Open questions at the time
    • No receptor identified for prodepin
    • Activity species-specific, mechanism of the difference unknown
  2. 1995 Medium

    Demonstrated that the same gene encodes a peptide with opposite vascular action, defining the locus as a source of functionally divergent products.

    Evidence Isolated cat pulmonary artery ring contractility assay with adrenotensin (proADM153-185)

    PMID:7637545

    Open questions at the time
    • No receptor characterized for adrenotensin
    • Single vessel/species tested
  3. 1997 Medium

    Resolved which receptor class mediates ADM tissue effects by identifying CGRP(8-37)-sensitive binding sites distinct from CGRP receptors and showing functional modulation of uterine contraction.

    Evidence Radioligand competition binding and organ-bath contractility in rat uterus with CGRP(8-37) antagonism

    PMID:9165042

    Open questions at the time
    • Molecular identity of the binding site not defined
    • Functional consequence of pregnancy-associated 10-fold density increase not established
  4. 1998 High

    Mapped the structural determinants of ADM action by separating receptor binding (C-terminal sequence) from receptor activation (ring structure) in the aldosterone-suppressing response.

    Evidence Structure-activity study with ADM fragments, radioligand binding, and aldosterone secretion assay in human adrenocortical cells, antagonized by ADM(22-52)

    PMID:9877221

    Open questions at the time
    • Receptor subtype not molecularly resolved
    • Downstream signaling pathway for aldosterone inhibition not defined
  5. 2000 Medium

    Distinguished the ADM-specific receptor from the CGRP1 receptor in vivo by showing ADM(22-52), but not CGRP(8-37), reverses endotoxic hypotension.

    Evidence Rat LPS endotoxemia model with selective ADM(22-52) and CGRP(8-37) antagonists

    PMID:11210719

    Open questions at the time
    • Cellular source of ADM during endotoxemia not identified
    • Downstream vasodilatory mediator not defined in this model
  6. 2002 Medium

    Defined an autocrine/paracrine ADM system in human adrenal cortex coupling receptor expression to aldosterone suppression, proliferation, and anti-apoptosis.

    Evidence RT-PCR for pADM/L1-R/CRLR/RAMPs, protein detection, and functional secretion/proliferation/apoptosis assays with ADM(22-52) reversal in cultured ZG cells

    PMID:11786920

    Open questions at the time
    • Signaling pathways linking ADM to proliferation/apoptosis not delineated
    • Relative roles of L1-R vs CRLR/RAMP not separated
  7. 2003 High

    Dissected the dual vasodilatory mechanism of ADM, separating an endothelial NO–guanylyl cyclase arm from a smooth-muscle cAMP/PKA arm in a single vessel.

    Evidence Human thymic artery reactivity with endothelial denudation and inhibitors of NOS, guanylyl cyclase, adenylyl cyclase, PKA, plus CGRP(8-37)

    PMID:12529288

    Open questions at the time
    • Molecular receptor identity at each cell type not defined
    • Relative in vivo contribution of the two arms not quantified
  8. 2003 Medium

    Linked ADM and its receptor component to a pathological vascular state by showing coordinated upregulation of ADM and RAMP2 during VSMC calcification.

    Evidence Quantitative RT-PCR for ADM and RAMP2 mRNA and RIA for ADM protein in a β-glycerophosphate VSMC calcification model

    PMID:12668214

    Open questions at the time
    • No direct functional perturbation of ADM in calcification
    • Causal direction between calcification and ADM induction unresolved
  9. 2009 Medium

    Provided functional genetic evidence that an upstream ADM SNP alters promoter activity and correlates with paroxetine response.

    Evidence Luciferase reporter assay of rs11042725 plus expression analysis and pharmacogenetic association

    PMID:19636336

    Open questions at the time
    • Association is correlational, no mechanistic link to antidepressant action
    • Drug-specificity (paroxetine only) unexplained
  10. 2016 Medium

    Placed ADM's cytoprotective action upstream of PI3K/Akt by showing it reduces inflammation and apoptosis in LPS-challenged Leydig cells.

    Evidence LPS cytotoxicity model with TUNEL, immunoblot for Bax/Bcl-2/caspase-3/PARP/p-Akt, ROS and cytokine measurements

    PMID:27212810

    Open questions at the time
    • No ADM receptor-blocking experiment to confirm mechanism
    • Whether Akt activation is necessary not tested
  11. 2021 Medium

    Connected ADM to hypoxic signaling and trophoblast biology, showing HIF-1α-dependent induction and ADM-driven invasion via MMP/Rac1.

    Evidence HTR-8/SVneo hypoxia culture with siRNA, HIF-1α inhibitor YC-1, invasion assay, and expression analysis

    PMID:32997116

    Open questions at the time
    • Receptor mediating trophoblast effects not identified
    • Opposing ADM/ADM2 effects on HLA-G mechanistically unresolved
  12. 2022 Medium

    Established ADM as a determinant of glioma chemosensitivity under miR-1297 control, modulating Akt/Erk1/2 and Bax/Bcl-2.

    Evidence ADM knockdown and miR-1297 overexpression with viability/apoptosis assays, xenografts, immunoblotting, and validated miR-1297–ADM targeting

    PMID:36183123

    Open questions at the time
    • Receptor and ligand requirement for the survival effect not tested
    • Whether Akt/Erk1/2 changes are causal not established
  13. 2022 Medium

    Defined an anti-senescence role for ADM in stem cells by epistatic placement upstream of the miR-152/CCNA2 axis.

    Evidence Lentiviral ADM overexpression in DPSCs with miR-152 mimic/CCNA2 rescue, cell-cycle and senescence assays

    PMID:36310381

    Open questions at the time
    • Mechanism by which ADM suppresses miR-152 unknown
    • Receptor dependence of the anti-senescence effect not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular identities of the distinct ADM receptors operating across tissues and how a single peptide selects between vasodilatory, endocrine, and pro-survival signaling outputs remain unresolved.
  • No unified receptor-to-pathway map across vascular, adrenal, and tumor contexts
  • Mechanism of ADM coupling to miRNA networks unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-8953897 Cellular responses to stimuli 1

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 rat proADM22-41 (prodepin), a product of the ADM gene distinct from adrenomedullin itself, produces systemic vasodilation and increases cardiac output when injected intravenously in rats, but this activity is species-specific (no effect in rabbit, piglet, cat, or dog). In vivo hemodynamic measurements (systemic arterial pressure, systemic vascular resistance, cardiac output) following bolus i.v. injection in multiple anesthetized species Life sciences Medium 8196484
1995 proADM153-185 (termed 'adrenotensin'), another product of the ADM gene, produces concentration-dependent vasoconstriction in cat pulmonary arterial rings, opposite to the vasodilatory effect of ADM itself, indicating the ADM gene locus encodes peptides with divergent vascular activities. Isolated organ bath contractility assay on cat pulmonary artery rings with and without U46619 precontraction Life sciences Medium 7637545
1997 Pharmacologically distinct, specific ADM-binding sites (separate from CGRP-binding sites) are present in rat uterus; ADM attenuates galanin-induced uterine contractions and this effect is blocked by CGRP(8-37), establishing that ADM acts through CGRP(8-37)-sensitive receptors in this tissue. Binding site density increases 10-fold in pregnancy. Radioligand binding assays with 125I-ADM and 125I-CGRP, competition binding, isolated organ bath contractility assay, mRNA detection by RT-PCR Endocrinology Medium 9165042
1998 ADM inhibits angiotensin-II-stimulated aldosterone secretion from human adrenocortical zona glomerulosa cells via ADM(22-52)-sensitive receptors; the six-membered ring structure AND the C-terminal amino-acid sequence (but not the N-terminal sequence) are both required for ADM's antimineralocorticoid effect; the C-terminal sequence is needed for receptor binding while the ring structure is needed for receptor activation. Autoradiographic radioligand binding with 125I-ADM(1-52) and competition by ADM fragments; aldosterone secretion assay from dispersed human adrenocortical cells treated with ADM fragments and antagonist ADM(22-52) Life sciences High 9877221
2000 ADM plays a major role in LPS-induced hypotension in rats, acting through ADM(22-52)-sensitive receptors; the ADM receptor antagonist ADM(22-52) counteracted and reversed LPS-induced blood pressure lowering, whereas the selective CGRP1 receptor antagonist CGRP(8-37) was ineffective. In vivo rat model of LPS-induced endotoxemia; blood pressure measurements with pharmacological antagonists ADM(22-52) and CGRP(8-37) Life sciences Medium 11210719
2002 Human adrenal zona glomerulosa (ZG) cells express ADM, its precursor pADM mRNA, and ADM receptors of both L1-R and CRLR/RAMP2,3 subtypes; through activation of these receptors, ADM (10^-8 M) inhibits angiotensin-II- and K+-stimulated aldosterone secretion, increases cell proliferation, and decreases apoptosis; all effects are reversed by ADM receptor antagonist ADM(22-52), establishing an autocrine/paracrine ADM system in human adrenal cortex. RT-PCR for pADM, L1-R, CRLR, RAMPs 1-3; immunocytochemistry and RIA for ADM protein; aldosterone secretion assay; proliferation and apoptosis assays in cultured ZG cells International journal of molecular medicine Medium 11786920
2003 In human thymic arteries, ADM-induced vasodilation is mediated by two distinct mechanisms: (1) an endothelial ADM receptor signals through nitric oxide–guanylyl cyclase (responses attenuated by endothelial denudation and by NOS/guanylyl cyclase inhibitors), and (2) a smooth muscle CGRP receptor signals through cAMP/PKA. Both CGRP and ADM responses (but not PAMP responses) are attenuated by the CGRP1 receptor antagonist CGRP(8-37). Isolated human thymic artery vascular reactivity assay; endothelial denudation; pharmacological inhibitors of NOS (L-NAME), guanylyl cyclase (ODQ), adenylyl cyclase (SQ-22536), PKA (Rp-cAMPS), and CGRP(8-37) receptor antagonist American journal of physiology. Regulatory, integrative and comparative physiology High 12529288
2003 Calcified vascular smooth muscle cells (VSMCs) upregulate both ADM mRNA (by 78%) and RAMP2 mRNA (by 56%), and release more ADM protein; RAMP2 mRNA levels positively correlate with ADM mRNA levels in calcified VSMCs, suggesting coordinated upregulation of ADM and its receptor component during vascular calcification. Competitive quantitative RT-PCR for ADM mRNA and RAMP2 mRNA; RIA for ADM protein; in vitro calcification model of rat VSMCs with β-glycerophosphate; calcium content, alkaline phosphatase activity, and 45Ca2+ uptake measurements Peptides Medium 12668214
2009 A SNP (rs11042725) in the upstream flanking region of the ADM gene significantly alters ADM promoter activity in reporter gene assays, and this variant is associated with response to the antidepressant paroxetine (OR=0.075, P<0.001) but not to fluoxetine or citalopram, suggesting ADM expression level modulates paroxetine efficacy. Luciferase reporter gene assay for ADM promoter SNP functional effect; microarray and quantitative PCR for ADM expression after paroxetine treatment; pharmacogenetic association analysis The pharmacogenomics journal Medium 19636336
2016 ADM protects rat Leydig cells from LPS-induced inflammation and apoptosis; ADM pretreatment reduces ROS, pro-inflammatory cytokines (IL-1β, IL-6, NO, PGE2), and apoptosis markers (Bax, caspase-3, PARP), while promoting Bcl-2 and mitochondrial membrane potential; these effects are associated with increased p-Akt levels, placing ADM's protective signaling upstream of the PI3K/Akt pathway. Cell culture with LPS-induced cytotoxicity model; TUNEL assay; DNA fragmentation; Western blot and RT-PCR for Bcl-2, Bax, caspase-3, PARP, and p-Akt; ROS/MDA/GSH/LDH and cytokine measurements Mediators of inflammation Medium 27212810
2021 Under hypoxia, ADM expression in trophoblast cells is upregulated in an HIF-1α-dependent manner; treatment with ADM agonists reduces HIF-1α activity and enhances trophoblast invasion by altering MMP2, MMP9, and Rac1 expression; ADM also increases HLA-G expression under normoxia, while ADM2 or combined ADM/ADM2 treatment under hypoxia attenuates HLA-G expression. Trophoblast cell (HTR-8/SVneo) culture under hypoxia; siRNA knockdown; YC-1 HIF-1α inhibitor; invasion assay; RT-PCR and protein expression analysis of HIF-1α, MMP2, MMP9, Rac1, HLA-G, ADM, ADM2 Biology of reproduction Medium 32997116
2022 ADM knockdown in glioma cells enhances the suppressive effect of temozolomide (TMZ) on cell viability and promotes apoptosis; miR-1297 directly targets the ADM transcript (confirmed experimentally) and inhibits ADM expression; miR-1297 overexpression phenocopies ADM knockdown under TMZ treatment, and ADM knockdown partially rescues miR-1297 inhibition effects; mechanistically, ADM modulates Bax/Bcl-2 ratio, Akt phosphorylation, and Erk1/2 phosphorylation. CCK-8 cell viability; Annexin V apoptosis assay; JC-1 mitochondrial membrane potential; nude mouse tumor assay; immunoblotting for Akt, Erk1/2 phosphorylation and apoptosis proteins; bioinformatics prediction + experimental validation of miR-1297 targeting ADM Journal of translational medicine Medium 36183123
2022 Overexpression of ADM in human dental pulp stem cells (DPSCs) promotes cell cycle progression (increased G2/M ratio), reduces senescence markers (p53, P21WAF1, P16INK4A), and decreases ROS accumulation; mechanistically, ADM overexpression suppresses miR-152, which normally directly targets CCNA2 (Cyclin A2) to induce senescence; restoration of miR-152 reverses ADM's anti-senescence effects, and CCNA2 overexpression rescues the miR-152-induced senescence, placing ADM upstream of the miR-152/CCNA2 axis. Lentiviral ADM overexpression; transcriptome/microRNA profiling; luciferase reporter assay (miR-152 targeting CCNA2 3'-UTR implied); transfection of miR-152 mimic, pCDH-CCNA2, CCNA2 siRNA; senescence assays; flow cytometry for cell cycle; immunoblotting for p53, P21, P16 Cell cycle (Georgetown, Tex.) Medium 36310381

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 Reversal mechanism of multidrug resistance by verapamil: direct binding of verapamil to P-glycoprotein on specific sites and transport of verapamil outward across the plasma membrane of K562/ADM cells. Cancer research 386 2569930
1993 Apoptosis of lung cancer cells caused by some anti-cancer agents (MMC, CPT-11, ADM) is inhibited by bcl-2. Biochemical and biophysical research communications 169 8476431
2013 Chrysin enhances sensitivity of BEL-7402/ADM cells to doxorubicin by suppressing PI3K/Akt/Nrf2 and ERK/Nrf2 pathway. Chemico-biological interactions 161 23994249
2013 Apigenin sensitizes doxorubicin-resistant hepatocellular carcinoma BEL-7402/ADM cells to doxorubicin via inhibiting PI3K/Akt/Nrf2 pathway. Carcinogenesis 147 23563091
2017 The Presence of Interleukin-13 at Pancreatic ADM/PanIN Lesions Alters Macrophage Populations and Mediates Pancreatic Tumorigenesis. Cell reports 104 28514653
1997 Expression of adrenomedullin (ADM) and its binding sites in the rat uterus: increased number of binding sites and ADM messenger ribonucleic acid in 20-day pregnant rats compared with nonpregnant rats. Endocrinology 70 9165042
2017 Apigenin sensitizes BEL-7402/ADM cells to doxorubicin through inhibiting miR-101/Nrf2 pathway. Oncotarget 57 29137246
2016 Timosaponin A-III reverses multi-drug resistance in human chronic myelogenous leukemia K562/ADM cells via downregulation of MDR1 and MRP1 expression by inhibiting PI3K/Akt signaling pathway. International journal of oncology 54 26984633
2015 Involvement of miR-133a and miR-326 in ADM resistance of HepG2 through modulating expression of ABCC1. Journal of drug targeting 50 25714665
2012 miR-137 restoration sensitizes multidrug-resistant MCF-7/ADM cells to anticancer agents by targeting YB-1. Acta biochimica et biophysica Sinica 50 23178914
2000 Decitabine (5-Aza-2'-deoxycytidine) decreased DNA methylation and expression of MDR-1 gene in K562/ADM cells. Leukemia 49 11069027
2016 Protective Effect of Adrenomedullin on Rat Leydig Cells from Lipopolysaccharide-Induced Inflammation and Apoptosis via the PI3K/Akt Signaling Pathway ADM on Rat Leydig Cells from Inflammation and Apoptosis. Mediators of inflammation 47 27212810
1992 Establishment and characterization of doxorubicin-resistant human bladder cancer cell line, KK47/ADM. The Journal of urology 46 1353119
2002 Adrenomedullin and its receptors are expressed in the zona glomerulosa of human adrenal gland: evidence that ADM enhances proliferation and decreases apoptosis in cultured ZG cells. International journal of molecular medicine 45 11786920
2014 CXCL12/CXCR4 axis confers adriamycin resistance to human chronic myelogenous leukemia and oroxylin A improves the sensitivity of K562/ADM cells. Biochemical pharmacology 44 24858801
2016 Osthole shows the potential to overcome P-glycoprotein‑mediated multidrug resistance in human myelogenous leukemia K562/ADM cells by inhibiting the PI3K/Akt signaling pathway. Oncology reports 43 27109742
2011 Cathepsin B cleavable novel prodrug Ac-Phe-Lys-PABC-ADM enhances efficacy at reduced toxicity in treating gastric cancer peritoneal carcinomatosis: an experimental study. Cancer 43 22006342
2005 Evidence for functional redundancy between C. elegans ADAM proteins SUP-17/Kuzbanian and ADM-4/TACE. Developmental biology 43 16197940
1991 Sufficient levels of quinine in the serum circumvent the multidrug resistance of the human leukemic cell line K562/ADM. Cancer 41 1913513
2016 Porous nano-hydroxyapatite/collagen scaffold containing drug-loaded ADM-PLGA microspheres for bone cancer treatment. Journal of materials science. Materials in medicine 39 26975746
2016 HOXB4 knockdown reverses multidrug resistance of human myelogenous leukemia K562/ADM cells by downregulating P-gp, MRP1 and BCRP expression via PI3K/Akt signaling pathway. International journal of oncology 37 27779650
2023 Multifunctional ADM hydrogel containing endothelial cell-exosomes for diabetic wound healing. Materials today. Bio 35 38089434
2017 CDCA4, a downstream gene of the Nrf2 signaling pathway, regulates cell proliferation and apoptosis in the MCF‑7/ADM human breast cancer cell line. Molecular medicine reports 35 29257222
2015 Ganoderma lucidum derived ganoderenic acid B reverses ABCB1-mediated multidrug resistance in HepG2/ADM cells. International journal of oncology 35 25779097
2017 Glycometabolic adaptation mediates the insensitivity of drug-resistant K562/ADM leukaemia cells to adriamycin via the AKT-mTOR/c-Myc signalling pathway. Molecular medicine reports 34 28259993
1996 ADM-1, a protein with metalloprotease- and disintegrin-like domains, is expressed in syncytial organs, sperm, and sheath cells of sensory organs in Caenorhabditis elegans. Molecular biology of the cell 34 8970152
2009 Two overlapping antiparallel genes encoding the iron regulator DmdR1 and the Adm proteins control siderophore [correction of sedephore] and antibiotic biosynthesis in Streptomyces coelicolor A3(2). The FEBS journal 33 19664059
1995 Adrenotensin: an ADM gene product with the opposite effects of ADM. Life sciences 32 7637545
2017 CLDN6 enhances chemoresistance to ADM via AF-6/ERKs pathway in TNBC cell line MDAMB231. Molecular and cellular biochemistry 31 29159771
2012 Mitochondrial localization of P-glycoprotein in the human breast cancer cell line MCF-7/ADM and its functional characterization. Oncology reports 30 22307172
2014 Potential therapeutic targets for oral cancer: ADM, TP53, EGFR, LYN, CTLA4, SKIL, CTGF, CD70. PloS one 29 25029526
2008 Reversal effect of Ganoderma lucidum polysaccharide on multidrug resistance in K562/ADM cell line. Acta pharmacologica Sinica 29 18430371
2018 ADM Scaffolds Generate a Pro-regenerative Microenvironment During Full-Thickness Cutaneous Wound Healing Through M2 Macrophage Polarization via Lamtor1. Frontiers in physiology 28 29915541
2012 Identification of proteins differentially expressed in adriamycin-resistant (pumc-91/ADM) and parental (pumc-91) human bladder cancer cell lines by proteome analysis. Journal of cancer research and clinical oncology 28 23183654
1998 Inhibitory effect of adrenomedullin (ADM) on the aldosterone response of human adrenocortical cells to angiotensin-II: role of ADM(22-52)-sensitive receptors. Life sciences 28 9877221
2011 CdTe quantum dots with daunorubicin induce apoptosis of multidrug-resistant human hepatoma HepG2/ADM cells: in vitro and in vivo evaluation. Nanoscale research letters 27 21711951
1994 Comparative effects of quinine and cinchonine in reversing multidrug resistance on human leukemic cell line K562/ADM. Leukemia 27 8289482
2006 Induction of apoptosis in K562/ADM cells by gamma-linolenic acid involves lipid peroxidation and activation of caspase-3. Chemico-biological interactions 26 16857180
2014 Role and mechanisms of microRNA‑503 in drug resistance reversal in HepG2/ADM human hepatocellular carcinoma cells. Molecular medicine reports 25 25269574
2005 Arsenic trioxide overcomes apoptosis inhibition in K562/ADM cells by regulating vital components in apoptotic pathway. Pharmacological research 24 15979894
2008 Up-regulation of ADM and SEPX1 in the lymphoblastoid cells of patients in monozygotic twins discordant for schizophrenia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 23 18081029
2017 The cycloartane triterpenoid ADCX impairs autophagic degradation through Akt overactivation and promotes apoptotic cell death in multidrug-resistant HepG2/ADM cells. Biochemical pharmacology 22 29074104
2015 Annonaceous acetogenins reverses drug resistance of human hepatocellular carcinoma BEL-7402/5-FU and HepG2/ADM cell lines. International journal of clinical and experimental pathology 22 26617951
2023 Evaluation of the effect of 3D-bioprinted gingival fibroblast-encapsulated ADM scaffolds on keratinized gingival augmentation. Journal of periodontal research 21 37042165
2017 Activities of MSCs Derived from Transgenic Mice Seeded on ADM Scaffolds in Wound Healing and Assessment by Advanced Optical Techniques. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 21 28601875
2003 Anti-proliferative effect of the abl tyrosine kinase inhibitor STI571 on the P-glycoprotein positive K562/ADM cell line. Cancer letters 21 12963124
2022 miR-1297 sensitizes glioma cells to temozolomide (TMZ) treatment through targeting adrenomedullin (ADM). Journal of translational medicine 20 36183123
2019 Preparation of ADM/PRP freeze-dried dressing and effect of mice full-thickness skin defect model. Biomedical materials (Bristol, England) 20 30665205
2018 Resveratrol induces autophagic apoptosis via the lysosomal cathepsin D pathway in human drug-resistant K562/ADM leukemia cells. Experimental and therapeutic medicine 20 29456707
2016 Saikosaponin A, an active glycoside from Radix bupleuri, reverses P-glycoprotein-mediated multidrug resistance in MCF-7/ADR cells and HepG2/ADM cells. Xenobiotica; the fate of foreign compounds in biological systems 20 27123551
2015 Preliminary study of the effects of β-elemene on MCF-7/ADM breast cancer stem cells. Genetics and molecular research : GMR 20 25867381
2013 Inhibition of P-glycoprotein and glutathione S-transferase-pi mediated resistance by fluoxetine in MCF-7/ADM cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 23731711
2013 The effect of porcine ADM to improve the burn wound healing. International journal of clinical and experimental pathology 20 24228089
2009 Association of a functional polymorphism in the adrenomedullin gene (ADM) with response to paroxetine. The pharmacogenomics journal 20 19636336
2010 An armed oncolytic adenovirus ZD55-IL-24 combined with ADM or DDP demonstrated enhanced antitumor effect in lung cancer. Acta oncologica (Stockholm, Sweden) 19 19734998
2013 Tegillarca granosa extract Haishengsu (HSS) suppresses expression of mdr1, BCR/ABL and sorcin in drug-resistant K562/ADM tumors in mice. Advances in medical sciences 18 23729583
2003 Responses to human CGRP, ADM, and PAMP in human thymic arteries. American journal of physiology. Regulatory, integrative and comparative physiology 18 12529288
2018 TRIB2 knockdown as a regulator of chemotherapy resistance and proliferation via the ERK/STAT3 signaling pathway in human chronic myelogenous leukemia K562/ADM cells. Oncology reports 17 29436678
2018 Targeting glycometabolic reprogramming to restore the sensitivity of leukemia drug-resistant K562/ADM cells to adriamycin. Life sciences 17 30473023
2014 Acerinol, a cyclolanstane triterpenoid from Cimicifuga acerina, reverses ABCB1-mediated multidrug resistance in HepG2/ADM and MCF-7/ADR cells. European journal of pharmacology 17 24704556
2012 Antitumor effect of arsenic trioxide in human K562 and K562/ADM cells by autophagy. Toxicology mechanisms and methods 17 22519831
2012 Suppression of BCRP expression and restoration of sensitivity to chemotherapy in multidrug-resistant HCC cell line HEPG2/ADM by RNA interference. Hepato-gastroenterology 17 23435138
2022 Identification of Inflammation-Related Biomarker Pro-ADM for Male Patients With Gout by Comprehensive Analysis. Frontiers in immunology 16 35116032
2015 Silencing clusterin gene transcription on effects of multidrug resistance reversing of human hepatoma HepG2/ADM cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 16 25600802
2015 shRNA-mediated silencing of sorcin increases drug chemosensitivity in myeloma KM3/DDP and U266/ADM cell lines. International journal of clinical and experimental pathology 16 26045737
2024 FASN contributes to ADM resistance of diffuse large B-cell lymphoma by inhibiting ferroptosis via nf-κB/STAT3/GPX4 axis. Cancer biology & therapy 15 39345091
2021 Altered expression of ADM and ADM2 by hypoxia regulates migration of trophoblast and HLA-G expression†. Biology of reproduction 15 32997116
2020 MicroRNA‑145 promotes the apoptosis of leukemic stem cells and enhances drug‑resistant K562/ADM cell sensitivity to adriamycin via the regulation of ABCE1. International journal of molecular medicine 15 32945355
2015 Plasma Adrenomedullin and Allelic Variation in the ADM Gene and Kidney Disease in People With Type 2 Diabetes. Diabetes 15 25948679
2015 Induction of apoptosis and reversal of permeability glycoprotein-mediated multidrug resistance of MCF-7/ADM by ginsenoside Rh2. International journal of clinical and experimental pathology 15 26191135
2013 The role of phenethyl isothiocyanate on bladder cancer ADM resistance reversal and its molecular mechanism. Anatomical record (Hoboken, N.J. : 2007) 15 23495258
2013 Knockdown of CD44 enhances chemosensitivity of acute myeloid leukemia cells to ADM and Ara-C. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 24375249
2010 Comparison of the multi-drug resistant human hepatocellular carcinoma cell line Bel-7402/ADM model established by three methods. Journal of experimental & clinical cancer research : CR 15 20727186
2004 [Reversal of resistance to adriamycin in human breast cancer cell line MCF-7/ADM by beta-elemene]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 15 15312359
2000 Adrenomedullin (ADM), acting through ADM(22-52)-sensitive receptors, is involved in the endotoxin-induced hypotension in rats. Life sciences 15 11210719
2023 A biotin-stabilized HKUST-1/ADM scaffold for facilitating MSC endothelial differentiation and vascularization in diabetic wound healing. Biomaterials science 14 36515094
2011 Synergistic effect of hyperthermia and neferine on reverse multidrug resistance in adriamycin-resistant SGC7901/ADM gastric cancer cells. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 14 21823010
2010 Establishment and identification of the human multi-drug-resistant cholangiocarcinoma cell line QBC939/ADM. Molecular biology reports 14 20111907
2022 An unexpected role for the conserved ADAM-family metalloprotease ADM-2 in Caenorhabditis elegans molting. PLoS genetics 13 35639786
2019 Safety and efficacy of l-lysine monohydrochloride and concentrated liquid l-lysine (base) produced by fermentation using Corynebacterium glutamicum strain NRRL B-50775 for all animal species based on a dossier submitted by ADM. EFSA journal. European Food Safety Authority 13 32626082
2015 Primary chicken embryo fibroblasts seeded acellular dermal matrix (3-D ADM) improve regeneration of full thickness skin wounds in rats. Tissue & cell 13 25907656
2013 Sex-specific effects of NLRP6/AVR and ADM loci on susceptibility to essential hypertension in a Sardinian population. PloS one 13 24147025
2003 Changes in amount of ADM mRNA and RAMP2 mRNA in calcified vascular smooth muscle cells. Peptides 13 12668214
2018 MiR-203 over-expression promotes prostate cancer cell apoptosis and reduces ADM resistance. European review for medical and pharmacological sciences 12 29949147
2017 Synergistic Effect of Baicalin and Adriamycin in Resistant HL-60/ADM Leukaemia Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 12 28869936
2016 Upregulating miR-146a by physcion reverses multidrug resistance in human chronic myelogenous leukemia K562/ADM cells. American journal of cancer research 12 27904770
2020 Total Saponins from Paris forrestii Reverse Multidrug Resistance of MCF-7/ADM Cells by Suppression of P-gp via ERK Signaling Pathway. Biological & pharmaceutical bulletin 11 32963175
2019 AML‑derived mesenchymal stem cells upregulate CTGF expression through the BMP pathway and induce K562‑ADM fusiform transformation and chemoresistance. Oncology reports 11 31322275
2016 Knockdown of HOXA10 reverses the multidrug resistance of human chronic mylogenous leukemia K562/ADM cells by downregulating P-gp and MRP-1. International journal of molecular medicine 11 27035504
2013 Reversal effect of arsenic sensitivity in human leukemia cell line K562 and K562/ADM using realgar transforming solution. Biological & pharmaceutical bulletin 11 23358330
2012 Effect of phosphatase and tensin homology deleted on chromosome 10 (PTEN) gene transfection on reversal of multidrug resistance in K562/ADM cells. Leukemia & lymphoma 11 22185283
2023 Reconstruction of Abdominal Wall Defect with Composite Scaffold of 3D Printed ADM/PLA in a Rat Model. Macromolecular bioscience 10 36746773
2023 Direct observation of the effects of chemical fixation in MNT-1 cells: A SE-ADM and Raman study. Proceedings of the National Academy of Sciences of the United States of America 10 38091295
2021 MicroRNA-18a-5p regulates the Warburg effect by targeting hypoxia-inducible factor 1α in the K562/ADM cell line. Experimental and therapeutic medicine 10 34447462
2017 The effect of miR-224 down-regulation on SW80 cell proliferation and apoptosis and weakening of ADM drug resistance. European review for medical and pharmacological sciences 10 29164556
2010 Tegillarca granosa extract Haishengsu inhibits the expression of P-glycoprotein and induces apoptosis in drug-resistant K562/ADM cells. Pharmaceutical biology 10 20645795
1994 Prodepin: a new product of the adrenomedullin (ADM) gene has systemic vasodilator activity. Life sciences 10 8196484
2022 Overexpression of adrenomedullin (ADM) alleviates the senescence of human dental pulp stem cells by regulating the miR-152/CCNA2 pathway. Cell cycle (Georgetown, Tex.) 9 36310381
2018 Solanine reverses multidrug resistance in human myelogenous leukemia K562/ADM cells by downregulating MRP1 expression. Oncology letters 9 29928376
1997 Adriamycin (ADM) induced apoptosis in transitional cell cancer (TCC) cell lines accompanied by p21 WAF1/CIP1 induction. Apoptosis : an international journal on programmed cell death 9 14646556

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