NLRP3: a key regulator of skin wound healing and macrophage-fibroblast interactions in mice
Abstract Wound healing is a highly coordinated process driven by intricate molecular signaling and dynamic interactions between diverse cell types. Nod-like receptor pyrin domain-containing protein 3 (NLRP3) has been implicated in the regulation of inflammation and tissue repair; however, its specif...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-025-02063-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571483757477888 |
|---|---|
| author | Jiamin Zhao Shuangyi Zhang Zhiguo Gong Wei Mao Wenhui Bao Qianru Li Yunjie Bai Feifei Gao Shuang Feng |
| author_facet | Jiamin Zhao Shuangyi Zhang Zhiguo Gong Wei Mao Wenhui Bao Qianru Li Yunjie Bai Feifei Gao Shuang Feng |
| author_sort | Jiamin Zhao |
| collection | DOAJ |
| description | Abstract Wound healing is a highly coordinated process driven by intricate molecular signaling and dynamic interactions between diverse cell types. Nod-like receptor pyrin domain-containing protein 3 (NLRP3) has been implicated in the regulation of inflammation and tissue repair; however, its specific role in skin wound healing remains unclear. This study highlights the pivotal role of NLRP3 in effective skin wound healing, as demonstrated by delayed wound closure and altered cellular and molecular responses in NLRP3-deficient (NLRP3−/−) mice. Histological analysis revealed impaired healing processes, accompanied by reduced expression of key inflammatory mediators, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2). Deficiencies in apoptosis were evident through altered expression of cysteine-aspartic acid protease 3 (Caspase-3), P53, and B-cell lymphoma-2 (Bcl-2). Furthermore, critical growth factors such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and matrix metalloproteinase-9 (MMP-9) were significantly decreased at the excisional skin wound sites. Furthermore, using co-culture systems, we found that NLRP3 mediated the interaction between macrophages and myofibroblasts. Wild-type fibroblast-conditioned media (MFbCM) enhanced nitric oxide (NO), IL-6, and tumor necrosis factor-α (TNF-α) production in M1 macrophages and arginase activity, chitinase 3-like protein 1 (Ym1), and IL-10 expression in M2 macrophages, effects significantly diminished with NLRP3−/− MFbCM. Similarly, conditioned media from wild-type M1 or M2 macrophages promoted the expression of FGF-2, VEGF, and MMP-2 expression in myofibroblasts, which was attenuated when using NLRP3−/− macrophage-conditioned media. PGE2 levels were reduced in both NLRP3−/− macrophages and myofibroblasts. Supplementing NLRP3−/− conditioned media with PGE2 partially restored the impaired functions, suggesting that PGE2 acts as a downstream mediator of NLRP3-regulated macrophage-myofibroblast interactions. These findings indicate that NLRP3 is a key regulator of skin wound healing, facilitating macrophage-myofibroblast communication. |
| format | Article |
| id | doaj-art-e6f75a268cf14129a4f62df2316cc4ef |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-e6f75a268cf14129a4f62df2316cc4ef2025-02-02T12:34:29ZengBMCCell Communication and Signaling1478-811X2025-01-0123111910.1186/s12964-025-02063-9NLRP3: a key regulator of skin wound healing and macrophage-fibroblast interactions in miceJiamin Zhao0Shuangyi Zhang1Zhiguo Gong2Wei Mao3Wenhui Bao4Qianru Li5Yunjie Bai6Feifei Gao7Shuang Feng8Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityLaboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityLaboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityLaboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityLaboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityLaboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityLaboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityLaboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityLaboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityAbstract Wound healing is a highly coordinated process driven by intricate molecular signaling and dynamic interactions between diverse cell types. Nod-like receptor pyrin domain-containing protein 3 (NLRP3) has been implicated in the regulation of inflammation and tissue repair; however, its specific role in skin wound healing remains unclear. This study highlights the pivotal role of NLRP3 in effective skin wound healing, as demonstrated by delayed wound closure and altered cellular and molecular responses in NLRP3-deficient (NLRP3−/−) mice. Histological analysis revealed impaired healing processes, accompanied by reduced expression of key inflammatory mediators, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2). Deficiencies in apoptosis were evident through altered expression of cysteine-aspartic acid protease 3 (Caspase-3), P53, and B-cell lymphoma-2 (Bcl-2). Furthermore, critical growth factors such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and matrix metalloproteinase-9 (MMP-9) were significantly decreased at the excisional skin wound sites. Furthermore, using co-culture systems, we found that NLRP3 mediated the interaction between macrophages and myofibroblasts. Wild-type fibroblast-conditioned media (MFbCM) enhanced nitric oxide (NO), IL-6, and tumor necrosis factor-α (TNF-α) production in M1 macrophages and arginase activity, chitinase 3-like protein 1 (Ym1), and IL-10 expression in M2 macrophages, effects significantly diminished with NLRP3−/− MFbCM. Similarly, conditioned media from wild-type M1 or M2 macrophages promoted the expression of FGF-2, VEGF, and MMP-2 expression in myofibroblasts, which was attenuated when using NLRP3−/− macrophage-conditioned media. PGE2 levels were reduced in both NLRP3−/− macrophages and myofibroblasts. Supplementing NLRP3−/− conditioned media with PGE2 partially restored the impaired functions, suggesting that PGE2 acts as a downstream mediator of NLRP3-regulated macrophage-myofibroblast interactions. These findings indicate that NLRP3 is a key regulator of skin wound healing, facilitating macrophage-myofibroblast communication.https://doi.org/10.1186/s12964-025-02063-9NLRP3Prostaglandin E2MacrophageMyofibroblastWound healing |
| spellingShingle | Jiamin Zhao Shuangyi Zhang Zhiguo Gong Wei Mao Wenhui Bao Qianru Li Yunjie Bai Feifei Gao Shuang Feng NLRP3: a key regulator of skin wound healing and macrophage-fibroblast interactions in mice Cell Communication and Signaling NLRP3 Prostaglandin E2 Macrophage Myofibroblast Wound healing |
| title | NLRP3: a key regulator of skin wound healing and macrophage-fibroblast interactions in mice |
| title_full | NLRP3: a key regulator of skin wound healing and macrophage-fibroblast interactions in mice |
| title_fullStr | NLRP3: a key regulator of skin wound healing and macrophage-fibroblast interactions in mice |
| title_full_unstemmed | NLRP3: a key regulator of skin wound healing and macrophage-fibroblast interactions in mice |
| title_short | NLRP3: a key regulator of skin wound healing and macrophage-fibroblast interactions in mice |
| title_sort | nlrp3 a key regulator of skin wound healing and macrophage fibroblast interactions in mice |
| topic | NLRP3 Prostaglandin E2 Macrophage Myofibroblast Wound healing |
| url | https://doi.org/10.1186/s12964-025-02063-9 |
| work_keys_str_mv | AT jiaminzhao nlrp3akeyregulatorofskinwoundhealingandmacrophagefibroblastinteractionsinmice AT shuangyizhang nlrp3akeyregulatorofskinwoundhealingandmacrophagefibroblastinteractionsinmice AT zhiguogong nlrp3akeyregulatorofskinwoundhealingandmacrophagefibroblastinteractionsinmice AT weimao nlrp3akeyregulatorofskinwoundhealingandmacrophagefibroblastinteractionsinmice AT wenhuibao nlrp3akeyregulatorofskinwoundhealingandmacrophagefibroblastinteractionsinmice AT qianruli nlrp3akeyregulatorofskinwoundhealingandmacrophagefibroblastinteractionsinmice AT yunjiebai nlrp3akeyregulatorofskinwoundhealingandmacrophagefibroblastinteractionsinmice AT feifeigao nlrp3akeyregulatorofskinwoundhealingandmacrophagefibroblastinteractionsinmice AT shuangfeng nlrp3akeyregulatorofskinwoundhealingandmacrophagefibroblastinteractionsinmice |