Lysine hydroxylase 1 (PLOD1) regulates glucose metabolism and promotes Th17 cell differentiation in psoriasis
Main Article Content
Keywords
Psoriasis, PLOD1, glycolysis, Th17 cells, PI3K/AKT/mTOR pathway
Abstract
Psoriasis is a common and chronic inflammatory skin disease. To treat psoriasis, more effective molecular targets still need to be developed and the mechanisms elucidated. PLOD1, as one of the genes related to glycolysis, can promote the glycolysis of cells. However, it is not clear whether upregulation of PLOD1 plays a causal role or is directly involved in psoriasis. Herein, we have examined the PLOD1 expression in patients with psoriasis and analyzed its effect on the progression of psoriasis. We found that PLOD1 is highly expressed in psoriasis. Also, the role of PLOD1 in promoting Th17 cell differentiation was further revealed, and PLOD1 promotes T cell glycolysis. Mechanically, PLOD1 activates the PI3K/AKT/mTOR pathway and thereby affects the progression of psoriasis. In conclusion, PLOD1 regulates glucose metabolism and promotes Th17 cell differentiation, which affects the progression of psoriasis.
References
1 Lee BW and Moon SJ. Inflammatory cytokines in psoriatic arthritis: Understanding pathogenesis and implications for treatment. Int. J. Mol. Sci. 2023;24(14). 10.3390/ijms241411662
2 Snape SD, Wigger-Alberti W, Goehring UM. A phase I randomized trial to assess the effect on skin infiltrate thickness and tolerability of topical phosphodiesterase inhibitors in the treatment of psoriasis vulgaris using a modified psoriasis plaque test. Br. J. Dermatol. 2016;175(3):479–86. 10.1111/bjd.14634
3 Inzinger M, Wippel-Slupetzky K, Weger W, Richter L, Mlynek A, Fleischander B, et al. Survival and effectiveness of tumour necrosis factor-alpha inhibitors in the treatment of plaque psoriasis under daily life conditions: Report from the psoriasis registry Austria. ActaDV. 2016;96(2):207–12. 10.2340/00015555-2214
4 Gisondi P, Geat D, Conti A, Dapavo P, Piaserico S, De Simone C, et al. TNF-alpha inhibitors biosimilars as first line systemic treatment for moderate-to-severe chronic plaque psoriasis. Expert Rev. Clin. Immunol. 2020;16(6):591–8. 10.1080/1744666X.2020.1771182
5 Zhang Y, Jing D, Zhou G, Xiao Y, Shen M, Chen X, et al. Evidence of a causal relationship between vitamin D status and risk of psoriasis from the UK biobank study. Front. Nutr. 2022;9:807344. 10.3389/fnut.2022.807344
6 Shu X, Chen XX, Kang XD, Ran M, Wang YL, Zhao ZK, et al. Identification of potential key molecules and signaling pathways for psoriasis based on weighted gene co-expression network analysis. World J. Clin. Cases. 2022;10(18):5965–83. 10.12998/wjcc.v10.i18.5965
7 Klemens CA, Dissanayake LV, Levchenko V, Zietara A, Palygin O, Staruschenko A. Modulation of blood pressure regulatory genes in the Agtrap-Plod1 locus associated with a deletion in Clcn6. Physiol. Rep. 2022;10(15):e15417. 10.14814/phy2.15417
8 Zhang Y, Wu Y, Su X. PLOD1 promotes cell growth and aerobic glycolysis by regulating the SOX9/PI3K/Akt/mTOR signaling pathway in gastric cancer. Front. Biosci. (Landmark Ed). 2021;26(8):322–34. 10.52586/4946
9 Xu M, Fang S, Xie A. Posttranscriptional control of PLOD1 in adipose-derived stem cells regulates scar formation through altering macrophage polarization. Ann. Transl. Med. 2021;9(20):1573. 10.21037/atm-21-4978
10 Hu M, Wu Y, Yang C, Wang X, Wang W, Zhou L, et al. Novel long noncoding RNA lnc-URIDS delays diabetic wound healing by targeting Plod1. Diabetes. 2020;69(10):2144–56. 10.2337/db20-0147
11 Gisondi P, Bellinato F, Conti A, Dapavo P, Piaserico S, De Simone C, et al. Consensus on the place in therapy of TNF-alpha inhibitors in the treatment of patients with chronic plaque psoriasis. JEADV. 2020;34(9):e470–e2. 10.1111/jdv.16380
12 AbuHilal M, Walsh S, Shear N. The role of IL-17 in the pathogenesis of psoriasis and update on IL-17 inhibitors for the treatment of plaque psoriasis. JCMS. 2016;20(6):509–16. 10.1177/1203475416651605
13 Suzuki S, Ota Y, Sano R, Morimoto Y, Moriya T, Shiota M. Growing teratoma syndrome after surgery for ovarian immature teratoma. EJGO. 2022;43(1):115–22. 10.31083/j.ejgo4301017
14 Zhi L, Ustyugova IV, Chen X, Zhang Q, Wu MX. Enhanced Th17 differentiation and aggravated arthritis in IEX-1-deficient mice by mitochondrial reactive oxygen species-mediated signaling. J. Immunol. 2012;189(4):1639–47. 10.4049/jimmunol.1200528
15 Liu Z, Chen L, Xiong D, Zhan Y, Liu J, Ouyang L, et al. Salidroside affects the Th17/Treg cell balance in aplastic anemia via the STAT3/HIF-1alpha/RORgammat pathway. Redox Rep. 2023;28(1):2225868. 10.1080/13510002.2023.2225868
16 Manohar K, Mesfin FM, Liu J, Shelley WC, Brokaw JP, Markel TA. Effect of oral chondroitin sulfate supplementation on acute brain injury in a murine necrotizing enterocolitis model. JACS. 2023;238(1):82-98. 10.14814/phy2.15819
17 Hao HF, Liu LM, Pan CS, Wang CS, Gao YS, Fan JY, et al. Rhynchophylline ameliorates endothelial dysfunction via Src-PI3K/Akt-eNOS cascade in the cultured intrarenal arteries of spontaneous hypertensive rats. Front. Physiol. 2017;8:928. 10.3389/fphys.2017.00928
18 Osaki M, Oshimura M, Ito H. PI3K-Akt pathway: Its functions and alterations in human cancer. Apoptosis. 2004;9(6):667–76. 10.1023/B:APPT.0000045801.15585.dd
19 Yu Y, Zhang Y, Wang S, Liu W, Hao C, Wang W. Inhibition effects of patchouli alcohol against influenza a virus through targeting cellular PI3K/Akt and ERK/MAPK signaling pathways. J. Virol. 2019;16(1):163. 10.1186/s12985-019-1266-x
20 Luan Y, Ren KD, Luan Y, Chen X, Yang Y. Mitochondrial dynamics: Pathogenesis and therapeutic targets of vascular diseases. Front. Cardiovasc. Med. 2021;8:770574. 10.3389/fcvm.2021.770574
21 Lim PJ, Lindert U, Opitz L, Hausser I, Rohrbach M, Giunta C. Transcriptome profiling of primary skin fibroblasts reveal distinct molecular features between PLOD1-and FKBP14-Kyphoscoliotic Ehlers-Danlos syndrome. Genes. 2019;10(7):10070517. 10.3390/genes10070517
2 Snape SD, Wigger-Alberti W, Goehring UM. A phase I randomized trial to assess the effect on skin infiltrate thickness and tolerability of topical phosphodiesterase inhibitors in the treatment of psoriasis vulgaris using a modified psoriasis plaque test. Br. J. Dermatol. 2016;175(3):479–86. 10.1111/bjd.14634
3 Inzinger M, Wippel-Slupetzky K, Weger W, Richter L, Mlynek A, Fleischander B, et al. Survival and effectiveness of tumour necrosis factor-alpha inhibitors in the treatment of plaque psoriasis under daily life conditions: Report from the psoriasis registry Austria. ActaDV. 2016;96(2):207–12. 10.2340/00015555-2214
4 Gisondi P, Geat D, Conti A, Dapavo P, Piaserico S, De Simone C, et al. TNF-alpha inhibitors biosimilars as first line systemic treatment for moderate-to-severe chronic plaque psoriasis. Expert Rev. Clin. Immunol. 2020;16(6):591–8. 10.1080/1744666X.2020.1771182
5 Zhang Y, Jing D, Zhou G, Xiao Y, Shen M, Chen X, et al. Evidence of a causal relationship between vitamin D status and risk of psoriasis from the UK biobank study. Front. Nutr. 2022;9:807344. 10.3389/fnut.2022.807344
6 Shu X, Chen XX, Kang XD, Ran M, Wang YL, Zhao ZK, et al. Identification of potential key molecules and signaling pathways for psoriasis based on weighted gene co-expression network analysis. World J. Clin. Cases. 2022;10(18):5965–83. 10.12998/wjcc.v10.i18.5965
7 Klemens CA, Dissanayake LV, Levchenko V, Zietara A, Palygin O, Staruschenko A. Modulation of blood pressure regulatory genes in the Agtrap-Plod1 locus associated with a deletion in Clcn6. Physiol. Rep. 2022;10(15):e15417. 10.14814/phy2.15417
8 Zhang Y, Wu Y, Su X. PLOD1 promotes cell growth and aerobic glycolysis by regulating the SOX9/PI3K/Akt/mTOR signaling pathway in gastric cancer. Front. Biosci. (Landmark Ed). 2021;26(8):322–34. 10.52586/4946
9 Xu M, Fang S, Xie A. Posttranscriptional control of PLOD1 in adipose-derived stem cells regulates scar formation through altering macrophage polarization. Ann. Transl. Med. 2021;9(20):1573. 10.21037/atm-21-4978
10 Hu M, Wu Y, Yang C, Wang X, Wang W, Zhou L, et al. Novel long noncoding RNA lnc-URIDS delays diabetic wound healing by targeting Plod1. Diabetes. 2020;69(10):2144–56. 10.2337/db20-0147
11 Gisondi P, Bellinato F, Conti A, Dapavo P, Piaserico S, De Simone C, et al. Consensus on the place in therapy of TNF-alpha inhibitors in the treatment of patients with chronic plaque psoriasis. JEADV. 2020;34(9):e470–e2. 10.1111/jdv.16380
12 AbuHilal M, Walsh S, Shear N. The role of IL-17 in the pathogenesis of psoriasis and update on IL-17 inhibitors for the treatment of plaque psoriasis. JCMS. 2016;20(6):509–16. 10.1177/1203475416651605
13 Suzuki S, Ota Y, Sano R, Morimoto Y, Moriya T, Shiota M. Growing teratoma syndrome after surgery for ovarian immature teratoma. EJGO. 2022;43(1):115–22. 10.31083/j.ejgo4301017
14 Zhi L, Ustyugova IV, Chen X, Zhang Q, Wu MX. Enhanced Th17 differentiation and aggravated arthritis in IEX-1-deficient mice by mitochondrial reactive oxygen species-mediated signaling. J. Immunol. 2012;189(4):1639–47. 10.4049/jimmunol.1200528
15 Liu Z, Chen L, Xiong D, Zhan Y, Liu J, Ouyang L, et al. Salidroside affects the Th17/Treg cell balance in aplastic anemia via the STAT3/HIF-1alpha/RORgammat pathway. Redox Rep. 2023;28(1):2225868. 10.1080/13510002.2023.2225868
16 Manohar K, Mesfin FM, Liu J, Shelley WC, Brokaw JP, Markel TA. Effect of oral chondroitin sulfate supplementation on acute brain injury in a murine necrotizing enterocolitis model. JACS. 2023;238(1):82-98. 10.14814/phy2.15819
17 Hao HF, Liu LM, Pan CS, Wang CS, Gao YS, Fan JY, et al. Rhynchophylline ameliorates endothelial dysfunction via Src-PI3K/Akt-eNOS cascade in the cultured intrarenal arteries of spontaneous hypertensive rats. Front. Physiol. 2017;8:928. 10.3389/fphys.2017.00928
18 Osaki M, Oshimura M, Ito H. PI3K-Akt pathway: Its functions and alterations in human cancer. Apoptosis. 2004;9(6):667–76. 10.1023/B:APPT.0000045801.15585.dd
19 Yu Y, Zhang Y, Wang S, Liu W, Hao C, Wang W. Inhibition effects of patchouli alcohol against influenza a virus through targeting cellular PI3K/Akt and ERK/MAPK signaling pathways. J. Virol. 2019;16(1):163. 10.1186/s12985-019-1266-x
20 Luan Y, Ren KD, Luan Y, Chen X, Yang Y. Mitochondrial dynamics: Pathogenesis and therapeutic targets of vascular diseases. Front. Cardiovasc. Med. 2021;8:770574. 10.3389/fcvm.2021.770574
21 Lim PJ, Lindert U, Opitz L, Hausser I, Rohrbach M, Giunta C. Transcriptome profiling of primary skin fibroblasts reveal distinct molecular features between PLOD1-and FKBP14-Kyphoscoliotic Ehlers-Danlos syndrome. Genes. 2019;10(7):10070517. 10.3390/genes10070517
Article Sidebar
Published
Mar 1, 2025
Article Details
How to Cite
Yue, Z., Zhang, W., Zhu, G., Sun, H., & Jiang, C. (2025). Lysine hydroxylase 1 (PLOD1) regulates glucose metabolism and promotes Th17 cell differentiation in psoriasis. Allergologia Et Immunopathologia, 53(2), 74-81. https://doi.org/10.15586/aei.v53i2.1269
Section
Original Articles
How to Cite
Yue, Z., Zhang, W., Zhu, G., Sun, H., & Jiang, C. (2025). Lysine hydroxylase 1 (PLOD1) regulates glucose metabolism and promotes Th17 cell differentiation in psoriasis. Allergologia Et Immunopathologia, 53(2), 74-81. https://doi.org/10.15586/aei.v53i2.1269