Exploring transcriptomic mechanisms underlying pulmonary adaptation to diverse environments in Indian rams.
Animals
Lung
/ metabolism
India
Sheep
/ genetics
Transcriptome
/ genetics
Altitude
Adaptation, Physiological
/ genetics
Gene Expression Profiling
/ methods
Gene Regulatory Networks
Male
NF-kappa B
/ metabolism
Signal Transduction
/ genetics
Gene Expression Regulation
Cytokines
/ genetics
Sequence Analysis, RNA
/ methods
Changthangi sheep
Gene expression
Hypoxia
Ladakh
Lung
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
01 Nov 2024
01 Nov 2024
Historique:
received:
02
09
2024
accepted:
25
10
2024
medline:
1
11
2024
pubmed:
1
11
2024
entrez:
1
11
2024
Statut:
epublish
Résumé
The Changthangi sheep thrive at high altitudes in the cold desert regions of Ladakh, India while Muzaffarnagri sheep are well-suited to the low altitude plains of northern India. This study investigates the molecular mechanisms of pulmonary adaptation to diverse environments by analyzing gene expression profiles of lung tissues through RNA sequencing. Four biological replicates of lung tissue from each breed were utilized to generate the transcriptomic data. Differences in gene expression analysis revealed discrete expression profiles in lungs of each breed. In Changthangi sheep, genes related to immune responses, particularly cytokine signaling, were significantly enriched. Pathway analysis highlighted the activation of NF-kB signaling, a key mediator of inflammation and immune response. Additionally, the gene network analysis indicated a strong association between cytokine signaling, hypoxia-inducible factor (HIF) and NF-kB activation, suggesting a coordinated response to hypoxic stress in lungs of Changthangi sheep. In Muzaffarnagri sheep, the gene expression profiles were enriched for pathways related to energy metabolism, homeostasis and lung physiology. Key pathways identified include collagen formation and carbohydrate metabolism, both of which are crucial for maintaining lung function and structural integrity. Gene network analysis further reinforced this by revealing a strong connection between genes associated with lung structure and function. Our findings shed light on the valuable insights into gene expression mechanisms that enable these sheep breeds to adapt to their respective environments and contribute to a better understanding of high altitude adaptation in livestock.
Sections du résumé
BACKGROUND
BACKGROUND
The Changthangi sheep thrive at high altitudes in the cold desert regions of Ladakh, India while Muzaffarnagri sheep are well-suited to the low altitude plains of northern India. This study investigates the molecular mechanisms of pulmonary adaptation to diverse environments by analyzing gene expression profiles of lung tissues through RNA sequencing.
METHODS AND RESULTS
RESULTS
Four biological replicates of lung tissue from each breed were utilized to generate the transcriptomic data. Differences in gene expression analysis revealed discrete expression profiles in lungs of each breed. In Changthangi sheep, genes related to immune responses, particularly cytokine signaling, were significantly enriched. Pathway analysis highlighted the activation of NF-kB signaling, a key mediator of inflammation and immune response. Additionally, the gene network analysis indicated a strong association between cytokine signaling, hypoxia-inducible factor (HIF) and NF-kB activation, suggesting a coordinated response to hypoxic stress in lungs of Changthangi sheep. In Muzaffarnagri sheep, the gene expression profiles were enriched for pathways related to energy metabolism, homeostasis and lung physiology. Key pathways identified include collagen formation and carbohydrate metabolism, both of which are crucial for maintaining lung function and structural integrity. Gene network analysis further reinforced this by revealing a strong connection between genes associated with lung structure and function.
CONCLUSIONS
CONCLUSIONS
Our findings shed light on the valuable insights into gene expression mechanisms that enable these sheep breeds to adapt to their respective environments and contribute to a better understanding of high altitude adaptation in livestock.
Identifiants
pubmed: 39485559
doi: 10.1007/s11033-024-10067-w
pii: 10.1007/s11033-024-10067-w
doi:
Substances chimiques
NF-kappa B
0
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1111Subventions
Organisme : Department of Biotechnology, Ministry of Science and Technology, India
ID : JRF
Organisme : Indian Council of Agricultural Research
ID : Institutional
Organisme : Indian Council of Agricultural Research
ID : Institutional
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Ganai TA, Misra SS, Sheikh FD (2011) Description of Changthangi sheep of Ladakh. Indian J Small Rumin 17(1):32–40
Vasu M, Ahlawat S, Chhabra P, Sharma U, Arora R, Sharma R, Mir MA, Singh MK (2024) Genetic insights into fiber quality, coat color and adaptation in Changthangi and Muzzafarnagri sheep: A comparative skin transcriptome analysis. Gene 891:147826. https://doi.org/10.1016/j.gene.2023.147826
doi: 10.1016/j.gene.2023.147826
pubmed: 37748630
Arora R, Kaur M, Kumar A, Chhabra P, Mir MA, Ahlawat S, Singh MK, Sharma R, Gera R (2024) Skeletal muscle transcriptomics of sheep acclimated to cold desert and tropical regions identifies genes and pathways accentuating their diversity. Int J Biometeorol Adv online publication. https://doi.org/10.1007/s00484-024-02708-3
doi: 10.1007/s00484-024-02708-3
Gera R, Arora R, Chhabra P, Sharma U, Parsad R, Ahlawat S, Mir MA, Singh MK, Sharma R, Kumar R (2024) Comparative transcriptome analyses of cardiac tissue reveals differential gene expression profiles in sheep in response to altitudinal adaptation. Small Rumin Res 107330. https://doi.org/10.1016/j.smallrumres.2024.107330
Ge Q, Guo Y, Zheng W, Zhao S, Cai Y, Qi X (2021) Molecular mechanisms detected in yak lung tissue via transcriptome-wide analysis provide insights into adaptation to high altitudes. Sci Rep 11(1):7786. https://doi.org/10.1038/s41598-021-87420-7
doi: 10.1038/s41598-021-87420-7
pubmed: 33833362
pmcid: 8032655
Zhao P, Zhao F, Hu J, Wang J, Liu X, Zhao Z, Xi Q, Sun H, Li S, Luo Y (2022) Physiology and Transcriptomics Analysis Reveal the Contribution of Lungs on High-Altitude Hypoxia Adaptation in Tibetan Sheep. Front Physiol 13:885444. https://doi.org/10.3389/fphys.2022.885444
doi: 10.3389/fphys.2022.885444
pubmed: 35634140
pmcid: 9133604
Kaur M, Kumar A, Siddaraju NK, Fairoze MN, Chhabra P, Ahlawat S, Vijh RK, Yadav A, Arora R (2020) Differential expression of miRNAs in skeletal muscles of Indian sheep with diverse carcass and muscle traits. Sci Rep 10:16332. https://doi.org/10.1038/s41598-020-73071-7
doi: 10.1038/s41598-020-73071-7
pubmed: 33004825
pmcid: 7529745
Arora R, Siddaraju NK, Manjunatha SS, Sudarshan S, Fairoze MN, Kumar A, Chhabra P, Kaur M, Sreesujatha RM, Ahlawat S, Vijh RK (2021) Muscle transcriptome provides the first insight into the dynamics of gene expression with progression of age in sheep. Sci Rep 11(1):22360. https://doi.org/10.1038/s41598-021-01848-5
doi: 10.1038/s41598-021-01848-5
pubmed: 34785720
pmcid: 8595721
Kumar A, Kaur M, Ahlawat S, Sharma U, Singh MK, Singh KV, Chhabra P, Vijh RK, Yadav A, Arora R (2021) Transcriptomic diversity in longissimus thoracis muscles of Barbari and Changthangi goat breeds of India. Genomics 113(4):1639–1646. https://doi.org/10.1016/J.YGENO.2021.04.019
doi: 10.1016/J.YGENO.2021.04.019
pubmed: 33862183
Storz JF (2021) High-Altitude Adaptation: Mechanistic Insights from Integrated Genomics and Physiology. Mol Biol Evol 38(7):2677–2691. https://doi.org/10.1093/molbev/msab064
doi: 10.1093/molbev/msab064
pubmed: 33751123
pmcid: 8233491
Andrews S (2010) FastQC: a quality control tool for high throughput sequence data. http://www.bioinformatics.babraham.ac.uk/projects/fastqc
Pathan M, Keerthikumar S, Ang CS, Gangoda L, Quek CY, Williamson NA, Mouradov D, Sieber OM, Simpson RJ, Salim A, Bacic A, Hill AF, Stroud DA, Ryan MT, Agbinya JI, Mariadason JM, Burgess AW, Mathivanan S (2015) FunRich: An open access standalone functional enrichment and interaction network analysis tool. Proteomics 15(15):2597–2601. https://doi.org/10.1002/pmic.201400515
doi: 10.1002/pmic.201400515
pubmed: 25921073
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504. https://doi.org/10.1101/gr.1239303
doi: 10.1101/gr.1239303
pubmed: 14597658
pmcid: 403769
Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY (2014) cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol 8 Suppl 4(Suppl 4):S11. https://doi.org/10.1186/1752-0509-8-S4-S11
doi: 10.1186/1752-0509-8-S4-S11
Untergasser A, Cutcutache I, Koressaar T, Ye J, Faircloth BC, Remm M, Rozen SG (2012) Primer3–new capabilities and interfaces. Nucleic Acids Res 40(15):e115. https://doi.org/10.1093/nar/gks596
doi: 10.1093/nar/gks596
pubmed: 22730293
pmcid: 3424584
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4):402–408. https://doi.org/10.1006/meth.2001.1262
Yu L, Guan YJ, Gao Y, Wang X (2009) Rpl30 and Hmgb1 are required for neurulation in golden hamster. Int J Neurosci 119(8):1076–1090
doi: 10.1080/00207450802330504
pubmed: 19922340
pmcid: 2780443
Korbecki J, Kojder K, Barczak K, Simińska D, Gutowska I, Chlubek D, Baranowska-Bosiacka I (2020) Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor-A Literature Review. Int J Mol Sci 21(16):5647. https://doi.org/10.3390/ijms21165647
doi: 10.3390/ijms21165647
pubmed: 32781743
pmcid: 7460668
Korbecki J, Kojder K, Kapczuk P, Kupnicka P, Gawrońska-Szklarz B, Gutowska I, Chlubek D, Baranowska-Bosiacka I (2021) The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors-A Review of Literature. Int J Mol Sci 22(2):843. https://doi.org/10.3390/ijms22020843
doi: 10.3390/ijms22020843
pubmed: 33467722
pmcid: 7830156
Ishimoto N, Park JH, Kawakami K, Tajiri M, Mizutani K, Akashi S, Tame JRH, Inoue A, Park SY (2023) Structural basis of CXC chemokine receptor 1 ligand binding and activation. Nat Commun 14(1):4107. https://doi.org/10.1038/s41467-023-39799-2
doi: 10.1038/s41467-023-39799-2
pubmed: 37433790
pmcid: 10336096
Colgan SP, Furuta GT, Taylor CT (2020) Hypoxia and Innate Immunity: Keeping Up with the HIFsters. Annu Rev Immunol 38:341–363. https://doi.org/10.1146/annurev-immunol-100819-121537
doi: 10.1146/annurev-immunol-100819-121537
pubmed: 31961750
pmcid: 7924528
Banerjee D, Upadhyay RC, Chaudhary UB, Kumar R, Singh S, Ashutosh GJM, Polley S, Mukherjee A, Das TK, De S (2014) Seasonal variation in expression pattern of genes under HSP70: Seasonal variation in expression pattern of genes under HSP70 family in heat- and cold-adapted goats (Capra hircus). Cell Stress Chaperones 19(3):401–408. https://doi.org/10.1007/s12192-013-0469-0
doi: 10.1007/s12192-013-0469-0
pubmed: 24114386
Chakraborty D, Cui W, Rosario GX, Scott RL, Dhakal P, Renaud SJ, Tachibana M, Rumi MA, Mason CW, Krieg AJ, Soares MJ (2016) HIF-KDM3A-MMP12 regulatory circuit ensures trophoblast plasticity and placental adaptations to hypoxia. Proc Natl Acad Sci USA 113(46):E7212–E7221. https://doi.org/10.1073/pnas.1612626113
doi: 10.1073/pnas.1612626113
pubmed: 27807143
pmcid: 5135375
Porro F, Rosato-Siri M, Leone E, Costessi L, Iaconcig A, Tongiorgi E, Muro AF (2010) beta-adducin (Add2) KO mice show synaptic plasticity, motor coordination and behavioral deficits accompanied by changes in the expression and phosphorylation levels of the alpha- and gamma-adducin subunits. Genes Brain Behav 9(1):84–96. https://doi.org/10.1111/j.1601-183X.2009.00537.x
doi: 10.1111/j.1601-183X.2009.00537.x
pubmed: 19900187
Hasan F, Chiu Y, Shaw RM, Wang J, Yee C (2021) Hypoxia acts as an environmental cue for the human tissue-resident memory T cell differentiation program. JCI Insight 6(10):e138970. https://doi.org/10.1172/jci.insight.138970
doi: 10.1172/jci.insight.138970
pubmed: 34027895
pmcid: 8262358
Hirano A, Yumimoto K, Tsunematsu R, Matsumoto M, Oyama M, Kozuka-Hata H, Nakagawa T, Lanjakornsiripan D, Nakayama KI, Fukada Y (2013) FBXL21 regulates oscillation of the circadian clock through ubiquitination and stabilization of cryptochromes. Cell 152(5):1106–1118. https://doi.org/10.1016/j.cell.2013.01.054
doi: 10.1016/j.cell.2013.01.054
pubmed: 23452856
Cardozo T, Pagano M (2004) The SCF ubiquitin ligase: insights into a molecular machine. Nat Rev Mol Cell Biol 5(9):739–751. https://doi.org/10.1038/nrm1471
doi: 10.1038/nrm1471
pubmed: 15340381
Cas MD, Morano C, Ottolenghi S, Dicasillati R, Roda G, Samaja M, Paroni R (2022) Inside the Alterations of Circulating Metabolome in Antarctica: The Adaptation to Chronic Hypoxia. Front Physiol 13:819345. https://doi.org/10.3389/fphys.2022.819345
doi: 10.3389/fphys.2022.819345
pubmed: 35145434
pmcid: 8821919
Samanta D, Semenza GL (2016) Serine Synthesis Helps Hypoxic Cancer Stem Cells Regulate Redox. Cancer Res 76(22):6458–6462. https://doi.org/10.1158/0008-5472.CAN-16-1730
doi: 10.1158/0008-5472.CAN-16-1730
pubmed: 27811150
Mohapatra SR, Sadik A, Sharma S, Poschet G, Gegner HM, Lanz TV, Lucarelli P, Klingmüller U, Platten M, Heiland I, Opitz CA (2021) Hypoxia Routes Tryptophan Homeostasis Towards Increased Tryptamine Production. Front Immunol 12:590532. https://doi.org/10.3389/fimmu.2021.590532
doi: 10.3389/fimmu.2021.590532
pubmed: 33679737
pmcid: 7933006
Lucattelli M, Cavarra E, de Santi MM, Tetley TD, Martorana PA, Lungarella G (2003) Collagen phagocytosis by lung alveolar macrophages in animal models of emphysema. Eur Respir J 22(5):728–734. https://doi.org/10.1183/09031936.03.00047603
doi: 10.1183/09031936.03.00047603
pubmed: 14621076
Rinnankoski-Tuikka R, Silvennoinen M, Torvinen S, Hulmi JJ, Lehti M, Kivelä R, Reunanen H, Kainulainen H (2012) Effects of high-fat diet and physical activity on pyruvate dehydrogenase kinase-4 in mouse skeletal muscle. Nutr Metab (Lond) 9(1):53. https://doi.org/10.1186/1743-7075-9-53
doi: 10.1186/1743-7075-9-53
pubmed: 22682013
Safe S, Jin UH, Morpurgo B, Abudayyeh A, Singh M, Tjalkens RB (2016) Nuclear receptor 4A (NR4A) family - orphans no more. J Steroid Biochem Mol Biol 157:48–60. https://doi.org/10.1016/j.jsbmb.2015.04.016
doi: 10.1016/j.jsbmb.2015.04.016
pubmed: 25917081
Phelan DE, Shigemura M, Aldhafiri S, Mota C, Hall TJ, Sznajder JI, Murphy EP, Crean D, Cummins EP (2021) Transcriptional Profiling of Monocytes Deficient in Nuclear Orphan Receptors NR4A2 and NR4A3 Reveals Distinct Signalling Roles Related to Antigen Presentation and Viral Response. Front Immunol 12:676644. https://doi.org/10.3389/fimmu.2021.676644
doi: 10.3389/fimmu.2021.676644
pubmed: 34248958
pmcid: 8267906
Al-Nusaif M, Yang Y, Li S, Cheng C, Le W (2022) The role of NURR1 in metabolic abnormalities of Parkinson’s disease. Mol Neurodegener 17(1):46. https://doi.org/10.1186/s13024-022-00544-w
doi: 10.1186/s13024-022-00544-w
pubmed: 35761385
pmcid: 9235236
James IA, Chen CL, Huang G, Zhang HY, Velten M, Besner GE (2010) HB-EGF protects the lungs after intestinal ischemia/reperfusion injury. J Surg Res 163(1):86–95. https://doi.org/10.1016/j.jss.2010.03.062
doi: 10.1016/j.jss.2010.03.062
pubmed: 20599214
Hult EM, Gurczynski SJ, O’Dwyer DN, Zemans RL, Rasky A, Wang Y, Murray S, Crawford HC, Moore BB (2022) Myeloid-and epithelial-derived heparin-binding epidermal growth factor-like growth factor promotes pulmonary fibrosis. Am J Respir Cell Mol Biol 67(6):641–653. https://doi.org/10.1165/rcmb.2022-0174OC
doi: 10.1165/rcmb.2022-0174OC
pubmed: 36036796
pmcid: 9743186
O’Donnell JJ, Birukova AA, Beyer EC, Birukov KG (2014) Gap junction protein connexin43 exacerbates lung vascular permeability. PLoS ONE 9(6):e100931. https://doi.org/10.1371/journal.pone.0100931
doi: 10.1371/journal.pone.0100931
pubmed: 24967639
pmcid: 4072707
Sarieddine MZ, Scheckenbach KE, Foglia B, Maass K, Garcia I, Kwak BR, Chanson M (2009) Connexin43 modulates neutrophil recruitment to the lung. J Cell Mol Med 13(11–12):4560–4570. https://doi.org/10.1111/j.1582-4934.2008.00654.x
doi: 10.1111/j.1582-4934.2008.00654.x
pubmed: 19166484
pmcid: 4515071
Mullur R, Liu YY, Brent GA (2014) Thyroid hormone regulation of metabolism. Physiol Rev 94(2):355–382. https://doi.org/10.1152/physrev.00030.2013
doi: 10.1152/physrev.00030.2013
pubmed: 24692351
pmcid: 4044302
Siafakas NM, Salesiotou V, Filaditaki V, Tzanakis N, Thalassinos N, Bouros D (1992) Respiratory muscle strength in hypothyroidism. Chest 102(1):189–194. https://doi.org/10.1378/chest.102.1.189
doi: 10.1378/chest.102.1.189
pubmed: 1623751
Kahaly GJ, Nieswandt J, Wagner S, Schlegel J, Mohr-Kahaly S, Hommel G (1998) Ineffective cardiorespiratory function in hyperthyroidism. J Clin Endocrinol Metab 83(11):4075–4078. https://doi.org/10.1210/jcem.83.11.5275
doi: 10.1210/jcem.83.11.5275
pubmed: 9814494
Wang Z, Lu B, Wu M, Gu T, Xu M, Tang F, Zhang L, Bai S, Zhong S, Yang Q (2024) Reduced sensitivity to thyroid hormones is associated with lung function in euthyroid individuals. Heliyon 10(9):e30309. https://doi.org/10.1016/j.heliyon.2024.e30309
doi: 10.1016/j.heliyon.2024.e30309
pubmed: 38711649
pmcid: 11070858
Pyle CJ, Patel DF, Peiró T, Joulia R, Grabiec AM, Hussell T, Tavernier G, Simpson A, Pease J, Harker JA, Lloyd CM, Snelgrove RJ (2022) Matrix Metalloproteinase-12 Supports Pulmonary B Cell Follicle Formation and Local Antibody Responses During Asthma. Am J Respir Crit Care Med 206(11):1424–1428. https://doi.org/10.1164/rccm.202109-2082LE
doi: 10.1164/rccm.202109-2082LE
pubmed: 35944138
pmcid: 9746859
D’Ignazio L, Batie M, Rocha S (2017) Hypoxia and Inflammation in Cancer, Focus on HIF and NF-κB. Biomedicines 5(2):21. https://doi.org/10.3390/biomedicines5020021
doi: 10.3390/biomedicines5020021
pubmed: 28536364
pmcid: 5489807
Bae T, Hallis SP, Kwak MK (2024) Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer. Exp Mol Med 56(3):501–514. https://doi.org/10.1038/s12276-024-01180-8
doi: 10.1038/s12276-024-01180-8
pubmed: 38424190
pmcid: 10985007
Pan Y, Zvaritch E, Tupling AR, Rice WJ, de Leon S, Rudnicki M, McKerlie C, Banwell BL, MacLennan DH (2003) Targeted disruption of the ATP2A1 gene encoding the sarco(endo)plasmic reticulum Ca2 + ATPase isoform 1 (SERCA1) impairs diaphragm function and is lethal in neonatal mice. J Biol Chem 278(15):13367–13375. https://doi.org/10.1074/jbc.M213228200
doi: 10.1074/jbc.M213228200
pubmed: 12556521
Roy AL (2021) Role of the multifunctional transcription factor TFII-I in DNA damage repair. DNA Repair 106:103175. https://doi.org/10.1016/j.dnarep.2021.103175
doi: 10.1016/j.dnarep.2021.103175
pubmed: 34280590
Taubenheim J, Kortmann C, Fraune S (2021) Function and Evolution of Nuclear Receptors in Environmental-Dependent Postembryonic Development. Front Cell Dev Biol 9:653792. https://doi.org/10.3389/fcell.2021.653792
doi: 10.3389/fcell.2021.653792
pubmed: 34178983
pmcid: 8222990
Stefan G, Holger S, Andreas G, Andreas W, Gerda G, Ulf B (2008) Myh7 as a biomarker for ppara modulators
Zhang J, Tang M, Shang J (2024) PPARγ Modulators in Lung Cancer: Molecular Mechanisms, Clinical Prospects, and Challenges. Biomolecules 14(2):190. https://doi.org/10.3390/biom14020190
doi: 10.3390/biom14020190
pubmed: 38397426
pmcid: 10886696
Sun M, Chi G, Xu J, Tan Y, Xu J, Lv S, Xu Z, Xia Y, Li L, Li Y (2018) Extracellular matrix stiffness controls osteogenic differentiation of mesenchymal stem cells mediated by integrin α5. Stem Cell Res Ther 9(1):52. https://doi.org/10.1186/s13287-018-0798-0
doi: 10.1186/s13287-018-0798-0
pubmed: 29490668
pmcid: 5831741
Liu L, Stephens B, Bergman M, May A, Chiang T (2021) Role of Collagen in Airway Mechanics. Bioeng (Basel) 8(1):13. https://doi.org/10.3390/bioengineering8010013
doi: 10.3390/bioengineering8010013
Wei C, Cacavale RJ, Kehoe JJ, Thomas PE, Iba MM (2001) CYP1A2 is expressed along with CYP1A1 in the human lung. Cancer Lett 171(1):113–120. https://doi.org/10.1016/s0304-3835(00)00712-6
doi: 10.1016/s0304-3835(00)00712-6
pubmed: 11485833
Androutsopoulos VP, Tsatsakis AM, Spandidos DA (2009) Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention. BMC Cancer 9:187. https://doi.org/10.1186/1471-2407-9-187
doi: 10.1186/1471-2407-9-187
pubmed: 19531241
pmcid: 2703651
Hazinski TA, Noisin E, Hamon I, DeMatteo A (1995) Sheep lung cytochrome P4501A1 (CYP1A1): cDNA cloning and transcriptional regulation by oxygen tension. J Clin Invest 96(4):2083–2089. https://doi.org/10.1172/JCI118257
doi: 10.1172/JCI118257
pubmed: 7560103
pmcid: 185848