皮肤衰老和常见皮肤病中成纤维细胞异质性与功能的研究进展

doi:10.35541/cjd.20240283

Abstract

Abstract: 【Abstract】 Fibroblasts are an essential cell type in skin tissues. On the one hand, fibroblasts play a central role in tissue repair, maintaining skin health and integrity; on the other hand, they play diverse and complex roles in the pathogenesis of various skin diseases. In recent years, the development of single?cell RNA sequencing and other technologies has greatly promoted research on fibroblast heterogeneity and function, as reflected in developmental origins, anatomical locations and disease pathogenesis. This review summarizes the heterogeneity and function of fibroblasts in skin aging and common skin diseases, aiming to deepen the understanding of related mechanisms and provide insights for clinical diagnosis and treatment.

Key words: Fibroblasts, Skin aging, Skin diseases, Heterogeneity, Subgroup, Pathogenesis

Peng Lianqi, Zhou Nuoya, Dong Enzhu, Rao Zhenqi, Suo Huinan, Tao Juan. Advances in fibroblast heterogeneity and function in skin aging and common skin diseases[J]. Chinese Journal of Dermatology,2026,e20240283. doi:10.35541/cjd.20240283

References ［41］

［1］	Tomasek JJ, Gabbiani G, Hinz B, et al. Myofibroblasts and mechano⁃regulation of connective tissue remodelling［J］. Nat Rev Mol Cell Biol, 2002,3（5）:349⁃363. DOI: 10.1038/nrm809.
［2］	Hsu CK, Lin HH, Harn HI, et al. Mechanical forces in skin disorders［J］. J Dermatol Sci, 2018,90（3）:232⁃240. DOI: 10. 1016/j.jdermsci.2018.03.004.
［3］	Lendahl U, Muhl L, Betsholtz C. Identification, discrimination and heterogeneity of fibroblasts［J］. Nat Commun, 2022,13（1）:3409. DOI: 10.1038/s41467⁃022⁃30633⁃9.
［4］	Korosec A, Frech S, Gesslbauer B, et al. Lineage identity and location within the dermis determine the function of papillary and reticular fibroblasts in human skin［J］. J Invest Dermatol, 2019,139（2）:342⁃351. DOI: 10.1016/j.jid.2018.07.033.
［5］	Janson DG, Saintigny G, van Adrichem A, et al. Different gene expression patterns in human papillary and reticular fibroblasts［J］. J Invest Dermatol, 2012,132（11）:2565⁃2572. DOI: 10.1038/jid.2012.192.
［6］	Salzer MC, Lafzi A, Berenguer⁃Llergo A, et al. Identity noise and adipogenic traits characterize dermal fibroblast aging［J］. Cell, 2018,175（6）:1575⁃1590. DOI: 10.1016/j.cell.2018.10.012.
［7］	陈旭, 孔佩慧, 牛悦青. 真皮成纤维细胞产生的皮肤老化相关分泌蛋白的特征［J］. 中华皮肤科杂志, 2020,53（12）:1041⁃1043. DOI: 10.3760/cma.j.issn.0412⁃4030.2020.12.101.
［8］	Zou Z, Long X, Zhao Q, et al. A single⁃cell transcriptomic atlas of human skin aging［J］. Dev Cell, 2021,56（3）:383⁃397. DOI: 10.1016/j.devcel.2020.11.002.
［9］	Solé⁃Boldo L, Raddatz G, Schütz S, et al. Single⁃cell transcriptomes of the human skin reveal age⁃related loss of fibroblast priming［J］. Commun Biol, 2020,3（1）:188. DOI: 10. 1038/s42003⁃020⁃0922⁃4.
［10］	Ahlers J, Falckenhayn C, Holzscheck N, et al. Single⁃cell RNA profiling of human skin reveals age⁃related loss of dermal sheath cells and their contribution to a juvenile phenotype［J］. Front Genet, 2021,12:797747. DOI: 10.3389/fgene.2021.797747.
［11］	Ali⁃Bahar M, Bauer B, Tredget EE, et al. Dermal fibroblasts from different layers of human skin are heterogeneous in expression of collagenase and types Ⅰ and Ⅲ procollagen mRNA［J］. Wound Repair Regen, 2004,12（2）:175⁃182. DOI: 10.1111/j.1067⁃1927. 2004.012110.x.
［12］	Huang X, Gu S, Liu C, et al. CD39+ fibroblasts enhance myofibroblast activation by promoting IL⁃11 secretion in hypertrophic scars［J］. J Invest Dermatol, 2022,142（4）:1065⁃1076. DOI: 10.1016/j.jid.2021.07.181.
［13］	Ţuţuianu R, Roşca AM, Florea G, et al. Heterogeneity of human fibroblasts isolated from hypertrophic scar［J］. Rom J Morphol Embryol, 2019,60（3）:793⁃802.
［14］	Vorstandlechner V, Laggner M, Copic D, et al. The serine proteases dipeptidyl⁃peptidase 4 and urokinase are key molecules in human and mouse scar formation［J］. Nat Commun, 2021,12（1）:6242. DOI: 10.1038/s41467⁃021⁃26495⁃2.
［15］	Zhang MZ, Dong XH, Zhang WC, et al. A comparison of proliferation levels in normal skin, physiological scar and keloid tissue［J］. J Plast Surg Hand Surg, 2023,57（1⁃6）:122⁃128. DOI: 10.1080/2000656X.2021.2017294.
［16］	Chao H, Zheng L, Hsu P, et al. IL⁃13RA2 downregulation in fibroblasts promotes keloid fibrosis via JAK/STAT6 activation［J］. JCI Insight, 2023,8（6）:e157091. DOI: 10.1172/jci.insight. 157091.
［17］	桑鹏飞, 方明松, 李旋, 等. ROCK1基因对瘢痕疙瘩成纤维细胞增殖与迁移及相关分子表达的影响［J］. 中华皮肤科杂志, 2023,56（3）:222⁃228. DOI: 10.35541/cjd.20210675.
［18］	刘晨阳, 元星花, 支嘉慧, 等. 跨膜蛋白45A对瘢痕疙瘩成纤维细胞合成细胞外基质的影响［J］. 中华皮肤科杂志, 2023,56（7）:666⁃669. DOI: 10.35541/cjd.20220056.
［19］	Meng J, Wenbo B, Yujie C, et al. mTOR⁃dependent autophagy machinery is inhibited in fibroblasts of keloid［J］. Int J Dermatol Venereol, 2021,4（3）:174⁃181. DOI: 10.1097/JD9.0000000000 000185.
［20］	Serror K, Ferrero L, Boismal F, et al. Evidence of inter⁃ and intra⁃keloid heterogeneity through analysis of dermal fibroblasts: a new insight in deciphering keloid physiopathology［J］. Exp Dermatol, 2023,32（7）:1096⁃1107. DOI: 10.1111/exd.14817.
［21］	Luo S, Benathan M, Raffoul W, et al. Abnormal balance between proliferation and apoptotic cell death in fibroblasts derived from keloid lesions［J］. Plast Reconstr Surg, 2001,107（1）:87⁃96. DOI: 10.1097/00006534⁃200101000⁃00014.
［22］	韩冰玉, 雷铁池, 江珊, 等. 人真皮网状层成纤维细胞在瘢痕疙瘩皮损组织中的表达与分布［J］. 中华皮肤科杂志, 2021,54（6）:504⁃509. DOI: 10.35541/cjd.20200906.
［23］	Xin Y, Min P, Xu H, et al. CD26 upregulates proliferation and invasion in keloid fibroblasts through an IGF⁃1⁃induced PI3K/AKT/mTOR pathway［J］. Burns Trauma, 2020,8:tkaa025. DOI: 10.1093/burnst/tkaa025.
［24］	Deng CC, Hu YF, Zhu DH, et al. Single⁃cell RNA⁃seq reveals fibroblast heterogeneity and increased mesenchymal fibroblasts in human fibrotic skin diseases［J］. Nat Commun, 2021,12（1）:3709. DOI: 10.1038/s41467⁃021⁃24110⁃y.
［25］	Shim J, Oh SJ, Yeo E, et al. Integrated analysis of single⁃cell and spatial transcriptomics in keloids: highlights on fibrovascular interactions in keloid pathogenesis［J］. J Invest Dermatol, 2022,142（8）:2128⁃2139. DOI: 10.1016/j.jid.2022.01.017.
［26］	Kidzeru EB, Lebeko M, Sharma JR, et al. Immune cells and associated molecular markers in dermal fibrosis with focus on raised cutaneous scars［J］. Exp Dermatol, 2023,32（5）:570⁃587. DOI: 10.1111/exd.14734.
［27］	Jumper N, Hodgkinson T, Paus R, et al. Site⁃specific gene expression profiling as a novel strategy for unravelling keloid disease pathobiology［J］. PLoS One, 2017,12（3）:e0172955. DOI: 10.1371/journal.pone.0172955.
［28］	Sawamura S, Makino K, Ide M, et al. Elevated alpha 1（I） to alpha 2（I） collagen ratio in dermal fibroblasts possibly contributes to fibrosis in systemic sclerosis［J］. Int J Mol Sci, 2022,23（12）:6811. DOI: 10.3390/ijms23126811.
［29］	Scharffetter K, Lankat⁃Buttgereit B, Krieg T. Localization of collagen mRNA in normal and scleroderma skin by in⁃situ hybridization［J］. Eur J Clin Invest, 1988,18（1）:9⁃17. DOI: 10. 1111/j.1365⁃2362.1988.tb01158.x.
［30］	Manetti M, Romano E, Rosa I, et al. Endothelial⁃to⁃mesenchymal transition contributes to endothelial dysfunction and dermal fibrosis in systemic sclerosis［J］. Ann Rheum Dis, 2017,76（5）:924⁃934. DOI: 10.1136/annrheumdis⁃2016⁃210229.
［31］	Romano E, Rosa I, Fioretto BS, et al. The role of pro⁃fibrotic myofibroblasts in systemic sclerosis: from origin to therapeutic targeting［J］. Curr Mol Med, 2022,22（3）:209⁃239. DOI: 10. 2174/0929867328666210325102749.
［32］	Tabib T, Huang M, Morse N, et al. Myofibroblast transcriptome indicates SFRP2hi fibroblast progenitors in systemic sclerosis skin［J］. Nat Commun, 2021,12（1）:4384. DOI: 10.1038/s41467⁃021⁃24607⁃6.
［33］	Gur C, Wang SY, Sheban F, et al. LGR5 expressing skin fibroblasts define a major cellular hub perturbed in scleroderma［J］. Cell, 2022,185（8）:1373⁃1388. DOI: 10.1016/j.cell. 2022. 03.011.
［34］	Oyoshi MK, He R, Kanaoka Y, et al. Eosinophil⁃derived leukotriene C4 signals via type 2 cysteinyl leukotriene receptor to promote skin fibrosis in a mouse model of atopic dermatitis［J］. Proc Natl Acad Sci U S A, 2012,109（13）:4992⁃4997. DOI: 10.1073/pnas.1203127109.
［35］	Löwa A, Graff P, Kaessmeyer S, et al. Fibroblasts from atopic dermatitis patients trigger inflammatory processes and hyperproliferation in human skin equivalents［J］. J Eur Acad Dermatol Venereol, 2020,34（6）:e262⁃e265. DOI: 10.1111/jdv. 16240.
［36］	Morgner B, Tittelbach J, Wiegand C. Induction of psoriasis⁃ and atopic dermatitis⁃like phenotypes in 3D skin equivalents with a fibroblast⁃derived matrix［J］. Sci Rep, 2023,13（1）:1807. DOI: 10.1038/s41598⁃023⁃28822⁃7.
［37］	He H, Suryawanshi H, Morozov P, et al. Single⁃cell transcriptome analysis of human skin identifies novel fibroblast subpopulation and enrichment of immune subsets in atopic dermatitis［J］. J Allergy Clin Immunol, 2020,145（6）:1615⁃1628. DOI: 10.1016/j.jaci.2020.01.042.
［38］	Mitamura Y, Reiger M, Kim J, et al. Spatial transcriptomics combined with single⁃cell RNA⁃sequencing unravels the complex inflammatory cell network in atopic dermatitis［J］. Allergy, 2023,78（8）:2215⁃2231. DOI: 10.1111/all.15781.
［39］	Sieminska I, Pieniawska M, Grzywa TM. The immunology of psoriasis⁃current concepts in pathogenesis［J］. Clin Rev Allergy Immunol, 2024,66（2）:164⁃191. DOI: 10.1007/s12016⁃024⁃08991⁃7.
［40］	Ma F, Plazyo O, Billi AC, et al. Single cell and spatial sequencing define processes by which keratinocytes and fibroblasts amplify inflammatory responses in psoriasis［J］. Nat Commun, 2023,14（1）:3455. DOI: 10.1038/s41467⁃023⁃39020⁃4.
［41］	Gao Y, Yao X, Zhai Y, et al. Single cell transcriptional zonation of human psoriasis skin identifies an alternative immunoregulatory axis conducted by skin resident cells［J］. Cell Death Dis, 2021,12（5）:450. DOI: 10.1038/s41419⁃021⁃03724⁃6.

[1]	Dai Xiaoxi, Hu Yu, Chen Kun. Clinical research progress on sunscreens in photodermatoses [J]. Chinese Journal of Dermatology, 2026, 59(7): 691-694.
[2]	Zubaidanmu Aizezi¹, Yi Lei², Aikedai Yusufu³, Tursunnayi Manafu⁴, Liu Dandan⁴, Yang Yi⁵, Wang Xiaodong¹. Antioxidant and protective effects of M2 macrophage-derived exosomes against photoaging in human skin fibroblasts [J]. Chinese Journal of Dermatology, 2026, 59(7): 662-670.
[3]	Li Wei¹, Yao Xu². Research on atopic dermatitis in China: current status and future perspectives [J]. Chinese Journal of Dermatology, 2026, 59(6): 505-511.
[4]	Chen Tingnan, Liang Jingyao, Deng Shilin, Shu Zhirong, Zhang Xibao. Immunophenotypic switching between psoriasis and atopic dermatitis after biologic therapy: a systematic review of clinical features, mechanisms and management strategies [J]. Chinese Journal of Dermatology, 2026, 59(5): 474-481.
[5]	Xu Zhuohong, Zhou Huan, Hu Yu, Gu Heng. Balneotherapy in skin diseases [J]. Chinese Journal of Dermatology, 2026, 59(5): 482-485.
[6]	Chen Xue, Zhang Jianzhong. Chronic hand eczema: epidemiology, disease burden, pathogenesis, and management [J]. Chinese Journal of Dermatology, 2026, 59(4): 327-332.
[7]	Xue Shuyue, Li Tingting, Kang Xiaojing. Lipid metabolism in the occurrence, development, diagnosis and treatment of cutaneous malignancies [J]. Chinese Journal of Dermatology, 2026, 59(4): 379-382.
[8]	Zhou Yuting, Song Qinghua, Wang Wenhui. Susceptibility genes of generalized pustular psoriasis [J]. Chinese Journal of Dermatology, 2026, 0(3): 20240211-e20240211.
[9]	Yang Yuan, Deng Danqi. Early diagnosis and treatment of psoriatic arthritis [J]. Chinese Journal of Dermatology, 2026, 0(3): 20240376-e20240376.
[10]	Lei Liangxinwen, Wu Hao, Lu Zhong. Application of optical coherence tomography in cosmetic dermatology [J]. Chinese Journal of Dermatology, 2026, 59(3): 273-277.
[11]	Expert Group on the Interpretation of the "Chinese expert consensus on the clinical application of photobiomodulation therapy in dermatology （）", Laser Medicine Group, Chinese Society of Dermatology. Interpretation of the Chinese expert consensus on the clinical application of photobiomodulation therapy in dermatology （2025） [J]. Chinese Journal of Dermatology, 2026, 59(3): 208-212.
[12]	Liu Lihao, Hu Yu, Chen Kun. Clinical application and development of photobiomodulation in dermatology [J]. Chinese Journal of Dermatology, 2026, 59(3): 278-282.
[13]	Zhang Hanmei, Feng Suying. Gut, skin, and oral microbiota in autoimmune bullous diseases [J]. Chinese Journal of Dermatology, 2026, 0(3): 20220315-e20220315.
[14]	Wang Li, Wang Qianqiu, Zhang Ruili. Research progress in latent syphilis [J]. Chinese Journal of Dermatology, 2026, 59(3): 286-289.
[15]	Yan Shiyi, Suo Huinan, Tao Juan, Zhou Nuoya. Role of mechanical tension in the development of skin diseases [J]. Chinese Journal of Dermatology, 2026, 0(3): 20230638-e20230638.

Advances in fibroblast heterogeneity and function in skin aging and common skin diseases

PDF

PDF (Mobile)

Knowledge

Abstract

Cite this article

share this article

References ［41］

Related Articles 15

Metrics

Comments

Recommended 10