{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:18:16Z","timestamp":1760059096894,"version":"build-2065373602"},"reference-count":24,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Research Funds for the Central Universities","award":["3332021069","BK20210050","CIFMS-2021-I2M-1-001"],"award-info":[{"award-number":["3332021069","BK20210050","CIFMS-2021-I2M-1-001"]}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["3332021069","BK20210050","CIFMS-2021-I2M-1-001"],"award-info":[{"award-number":["3332021069","BK20210050","CIFMS-2021-I2M-1-001"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences","award":["3332021069","BK20210050","CIFMS-2021-I2M-1-001"],"award-info":[{"award-number":["3332021069","BK20210050","CIFMS-2021-I2M-1-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Psoriasis pathogenesis involves dysregulated immune responses, yet the role of protein prenylation (particularly PGGT1B-mediated geranylgeranylation) in macrophage-driven inflammation remains poorly understood. This study aims to explore the role and molecular mechanism of protein geranylgeranyltransferase type I subunit beta (PGGT1B) in the development of psoriasis. Myeloid cell-specific PGGT1B gene knockout mice were generated, and a mouse psoriasis model was established with imiquimod to study the role and mechanism of PGGT1B gene downregulation-induced macrophage activation in the pathogenesis of psoriasis. Bone marrow-derived macrophages (BMDMs) from wild-type and PGGT1B knockout mice were cultured and stimulated with resiquimod (R848) to simulate the immune microenvironment of psoriasis. In addition, the differentially expressed genes induced by PGGT1B knockout were analyzed using RNA-seq, and bioinformatics analysis was carried out to study the possible biological process of PGGT1B regulation. Finally, PMA-THP-1 was co-cultured with HaCaT cells to study the effect of PGGT1B deletion in macrophages on the proliferation and differentiation of keratinocytes. Bone marrow PGGT1B deficiency aggravated the psoriasis-like lesions induced by imiquimod in mice. In BMDMs with PGGT1B deficiency, the NF-\u03baB signaling pathway was over-activated by R848, and the expressions of proinflammatory cytokines IL-1\u03b2, IL-6, and TNF-\u03b1 were significantly increased. Activation of cell division cycle 42 (CDC42) may mediate the activation of the NF-\u03baB pathway in PGGT1B-deficient BMDMs. PGGT1B deletion can promote the proliferation and inhibit the differentiation of HaCaT cells. Reduced PGGT1B levels can increase the expression of CDC42, which further activates NLRP3 inflammation in macrophages through NF-\u03baB signaling, further aggravating the inflammatory state of psoriasis. Psoriasis-like lesions induced by IMQ are aggravated when PGGT1B expression is reduced in mouse bone marrow cells. A possible mechanism for this is that PGGT1B-deficient macrophages migrate to the epidermis more easily during psoriasis, which leads to the activation of Cdc42, NF-\u03baB signaling, and NLRP3 inflammatory corpuscles.<\/jats:p>","DOI":"10.3390\/ijms26104901","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T08:41:12Z","timestamp":1747730472000},"page":"4901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Myeloid PGGT1B Deficiency Promotes Psoriasiform Dermatitis by Promoting the Secretion of Inflammatory Factors"],"prefix":"10.3390","volume":"26","author":[{"given":"Shanshan","family":"Yu","sequence":"first","affiliation":[{"name":"Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangyuan","family":"Long","sequence":"additional","affiliation":[{"name":"Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuecui","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng","family":"Gu","sequence":"additional","affiliation":[{"name":"Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhimin","family":"Hao","sequence":"additional","affiliation":[{"name":"Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"m1590","DOI":"10.1136\/bmj.m1590","article-title":"Global Psoriasis A: National, regional, and worldwide epidemiologyof psoriasis: Systematic analysis and modelling study","volume":"369","author":"Parisi","year":"2020","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rendon, A., and Schakel, K. (2019). Psoriasis Pathogenesis and Treatment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061475"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1111\/bjd.18245","article-title":"Management of psoriasis as a systemic disease: What is the evidence?","volume":"182","author":"Korman","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.2147\/CCID.S420850","article-title":"Cellular Mechanisms of Psoriasis Pathogenesis: A Systemic Review","volume":"16","author":"Wu","year":"2023","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1001\/jama.2020.4006","article-title":"Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"170","DOI":"10.7861\/clinmed.2021-0257","article-title":"Psoriasis: A brief overview","volume":"21","author":"Raharja","year":"2021","journal-title":"Clin. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e14854","DOI":"10.1111\/dth.14854","article-title":"The diagnostic significance of PGGT1B in psoriasis","volume":"34","author":"Hao","year":"2021","journal-title":"Dermatol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1161\/CIRCULATIONAHA.112.000588","article-title":"Targeting GGTase-I activates RHOA, increases macrophage reverse cholesterol transport, and reduces atherosclerosis in mice","volume":"127","author":"Khan","year":"2013","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1136\/gutjnl-2021-325520","article-title":"Epithelial RAC1-dependent cytoskeleton dynamics controls cell mechanics, cell shedding and barrier integrity in intestinal inflammation","volume":"72","author":"Ngo","year":"2023","journal-title":"Gut"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1053\/j.gastro.2019.07.007","article-title":"Inhibiting PGGT1B Disrupts Function of RHOA, Resulting in T-cell Expression of Integrin alpha4beta7 and Development of Colitis in Mice","volume":"157","author":"Fastancz","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7574245","DOI":"10.1155\/2020\/7574245","article-title":"Geranylgeranyl Transferase-I Knockout Inhibits Oxidative Injury of Vascular Smooth Muscle Cells and Attenuates Diabetes-Accelerated Atherosclerosis","volume":"2020","author":"Chen","year":"2020","journal-title":"J. Diabetes Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3975","DOI":"10.1038\/s41467-019-11606-x","article-title":"Protein prenylation restrains innate immunity by inhibiting Rac1 effector interactions","volume":"10","author":"Akula","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gao, J., Chen, F., Fang, H., Mi, J., Qi, Q., and Yang, M. (2020). Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice. Biol. Res., 53.","DOI":"10.1186\/s40659-020-00316-0"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s12016-018-8702-3","article-title":"The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis","volume":"55","author":"Blauvelt","year":"2018","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Brembilla, N.C., Senra, L., and Boehncke, W.H. (2018). The IL-17 Family of Cytokines in Psoriasis: IL-17A and Beyond. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01682"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pondeljak, N., Lugovic-Mihic, L., Tomic, L., Parac, E., Pedic, L., and Lazic-Mosler, E. (2023). Key Factors in the Complex and Coordinated Network of Skin Keratinization. Their Significance and Involvement in Common Skin Conditions. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010236"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.jaci.2023.05.012","article-title":"Single-cell transcriptomics suggest distinct upstream drivers of IL-17A\/F in hidradenitis versus psoriasis","volume":"152","author":"Kim","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lee, B.W., and Moon, S.J. (2023). Inflammatory Cytokines in Psoriatic Arthritis: Understanding Pathogenesis and Implications for Treatment. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202306.2029.v1"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"418","DOI":"10.23736\/S0392-0488.18.06202-8","article-title":"Psoriasis and the TNF\/IL23\/IL17 axis","volume":"154","author":"Furue","year":"2019","journal-title":"G. Ital. Dermatol. Venereol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1111\/jgh.16321","article-title":"Low-intensity pulsed ultrasound at ST36 improves the gastric motility by TNF-alpha\/IKKbeta\/NF-kappaB signaling pathway in diabetic rats","volume":"38","author":"Han","year":"2023","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1248\/bpb.b21-00574","article-title":"LncRNA Snhg5 Attenuates Status Epilepticus Induced Inflammation through Regulating NF-kappaBeta Signaling Pathway","volume":"45","author":"Wang","year":"2022","journal-title":"Biol. Pharm. Bull."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.tcb.2015.11.003","article-title":"Cdc42 and Cellular Polarity: Emerging Roles at the Golgi","volume":"26","author":"Farhan","year":"2016","journal-title":"Trends Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"657","DOI":"10.2217\/bmm-2023-0425","article-title":"Longitudinal change in CDC42 in psoriasis: Correlation with disease activity and treatment response","volume":"17","author":"Xu","year":"2023","journal-title":"Biomark. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.jid.2021.06.019","article-title":"Mouse Models of Psoriasis: A Comprehensive Review","volume":"142","author":"Gangwar","year":"2022","journal-title":"J. Investig. Dermatol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/10\/4901\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:35:48Z","timestamp":1760031348000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/10\/4901"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,20]]},"references-count":24,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ijms26104901"],"URL":"https:\/\/doi.org\/10.3390\/ijms26104901","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,5,20]]}}}