Extracellular matrix and dermal nerve growth factor dysregulation in prurigo nodularis compared to atopic dermatitis
Prurigo nodularis (PN) is a chronic, pruritic, inflammatory skin disease characterized by hyperkeratotic nodules on the trunk and extremities. While there is growing research on the immunological basis of PN, the neuropathic and structural components of PN lesions are unknown. This study examines th...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.1022889/full |
| _version_ | 1811288784176676864 |
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| author | Junwen Deng Varsha Parthasarathy Melika Marani Zachary Bordeaux Kevin Lee Chi Trinh Hannah L. Cornman Anusha Kambala Thomas Pritchard Shihua Chen Nishadh Sutaria Olusola O. Oladipo Madan M. Kwatra Martin P. Alphonse Shawn G. Kwatra |
| author_facet | Junwen Deng Varsha Parthasarathy Melika Marani Zachary Bordeaux Kevin Lee Chi Trinh Hannah L. Cornman Anusha Kambala Thomas Pritchard Shihua Chen Nishadh Sutaria Olusola O. Oladipo Madan M. Kwatra Martin P. Alphonse Shawn G. Kwatra |
| author_sort | Junwen Deng |
| collection | DOAJ |
| description | Prurigo nodularis (PN) is a chronic, pruritic, inflammatory skin disease characterized by hyperkeratotic nodules on the trunk and extremities. While there is growing research on the immunological basis of PN, the neuropathic and structural components of PN lesions are unknown. This study examines the inflammatory, neuropathic, and structural pathways in PN compared to atopic dermatitis (AD) using RNA-sequencing of the lesional and non-lesional skin tissue of PN and AD patients, as well as immunohistochemistry analysis of nerve growth factor (NGF), a neurotrophic factor that regulates nerve development. Transcriptomic analysis of skin biopsies revealed that compared to lesional AD skin, lesional PN skin had significantly increased expression of NGF, matrix metalloproteinases, OSM, MCEMP1, IL1α, IL1β, CXCL2, CXCL5, CXCL8, and insulin-like growth factors in PN compared to AD, and decreased expression of CCL13, CCL26, EPHB1, and collagens (COL4/6). Gene set enrichment analysis demonstrated higher enrichment of keratinization, cornified envelope, myelin sheath, TGF-beta signaling, extracellular matrix disassembly, metalloendopeptidase activity, and neurotrophin-TRK receptor signaling pathways in PN. On immunohistochemistry, PN lesions demonstrated higher dermal NGF expression compared to AD. We present novel findings demonstrating increased neurotrophic and extracellular matrix remodeling signatures in PN compared to AD, possibly explaining the morphological differences in their lesions. These signatures may therefore be important components of the PN pathogenesis and may serve as therapeutic targets. |
| first_indexed | 2024-04-13T03:43:30Z |
| format | Article |
| id | doaj.art-517c5d4160ab47cd87f1c1b94ceb0e0d |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-13T03:43:30Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-517c5d4160ab47cd87f1c1b94ceb0e0d2022-12-22T03:04:05ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-12-01910.3389/fmed.2022.10228891022889Extracellular matrix and dermal nerve growth factor dysregulation in prurigo nodularis compared to atopic dermatitisJunwen Deng0Varsha Parthasarathy1Melika Marani2Zachary Bordeaux3Kevin Lee4Chi Trinh5Hannah L. Cornman6Anusha Kambala7Thomas Pritchard8Shihua Chen9Nishadh Sutaria10Olusola O. Oladipo11Madan M. Kwatra12Martin P. Alphonse13Shawn G. Kwatra14Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Anesthesiology, Duke University School of Medicine, Durham, NC, United StatesDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesPrurigo nodularis (PN) is a chronic, pruritic, inflammatory skin disease characterized by hyperkeratotic nodules on the trunk and extremities. While there is growing research on the immunological basis of PN, the neuropathic and structural components of PN lesions are unknown. This study examines the inflammatory, neuropathic, and structural pathways in PN compared to atopic dermatitis (AD) using RNA-sequencing of the lesional and non-lesional skin tissue of PN and AD patients, as well as immunohistochemistry analysis of nerve growth factor (NGF), a neurotrophic factor that regulates nerve development. Transcriptomic analysis of skin biopsies revealed that compared to lesional AD skin, lesional PN skin had significantly increased expression of NGF, matrix metalloproteinases, OSM, MCEMP1, IL1α, IL1β, CXCL2, CXCL5, CXCL8, and insulin-like growth factors in PN compared to AD, and decreased expression of CCL13, CCL26, EPHB1, and collagens (COL4/6). Gene set enrichment analysis demonstrated higher enrichment of keratinization, cornified envelope, myelin sheath, TGF-beta signaling, extracellular matrix disassembly, metalloendopeptidase activity, and neurotrophin-TRK receptor signaling pathways in PN. On immunohistochemistry, PN lesions demonstrated higher dermal NGF expression compared to AD. We present novel findings demonstrating increased neurotrophic and extracellular matrix remodeling signatures in PN compared to AD, possibly explaining the morphological differences in their lesions. These signatures may therefore be important components of the PN pathogenesis and may serve as therapeutic targets.https://www.frontiersin.org/articles/10.3389/fmed.2022.1022889/fullprurigo nodularisatopic dermatitispruritustranscriptomeimmunenerve growth factor |
| spellingShingle | Junwen Deng Varsha Parthasarathy Melika Marani Zachary Bordeaux Kevin Lee Chi Trinh Hannah L. Cornman Anusha Kambala Thomas Pritchard Shihua Chen Nishadh Sutaria Olusola O. Oladipo Madan M. Kwatra Martin P. Alphonse Shawn G. Kwatra Extracellular matrix and dermal nerve growth factor dysregulation in prurigo nodularis compared to atopic dermatitis Frontiers in Medicine prurigo nodularis atopic dermatitis pruritus transcriptome immune nerve growth factor |
| title | Extracellular matrix and dermal nerve growth factor dysregulation in prurigo nodularis compared to atopic dermatitis |
| title_full | Extracellular matrix and dermal nerve growth factor dysregulation in prurigo nodularis compared to atopic dermatitis |
| title_fullStr | Extracellular matrix and dermal nerve growth factor dysregulation in prurigo nodularis compared to atopic dermatitis |
| title_full_unstemmed | Extracellular matrix and dermal nerve growth factor dysregulation in prurigo nodularis compared to atopic dermatitis |
| title_short | Extracellular matrix and dermal nerve growth factor dysregulation in prurigo nodularis compared to atopic dermatitis |
| title_sort | extracellular matrix and dermal nerve growth factor dysregulation in prurigo nodularis compared to atopic dermatitis |
| topic | prurigo nodularis atopic dermatitis pruritus transcriptome immune nerve growth factor |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.1022889/full |
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