Hypoxic MSCs Reduce UV-B Collagen Loss by Modulating CD68 and TNF-α Expression
Abstrak
Ultraviolet-B (UV-B) radiation-induced skin photoaging is marked by collagen degradation and chronic inflammation, with limited effective treatments currently available. Hypoxic-preconditioned mesenchymal stem cells (H-MSCs) offer a novel therapeutic approach due to their immunomodulatory capabilities. This study evaluated the effects of H-MSCs at two doses (2.5×105 and 5×105 cells) on UVB-induced collagen loss, focusing on CD68 expression and TNF-α levels in a rat model. Male Wistar rats were divided into five groups: healthy controls, UV-B-exposed negative controls (saline), positive controls (hyaluronic acid), and two H-MSC-treated groups. After UV-B exposure (160 mJ/cm², five times per week for two weeks), validated H-MSCs were administered subcutaneously. Collagen content was assessed histologically, while CD68 gene expression and TNF-α levels were measured by qRT-PCR and ELISA, respectively. UVB exposure led to significant reductions in collagen and increased levels of inflammatory markers. H-MSC treatment showed dose-dependent anti-inflammatory effects, with the higher dose (5×105 cells) optimally reducing CD68 expression and TNF-α levels, nearly matching healthy controls. These results suggest that H-MSCs, particularly at higher doses, may be a promising therapy for UVB-induced skin damage and collagen loss.
Kata Kunci
Teks Lengkap:
PDF (English)Referensi
Siebenga PS, van Amerongen G, Klaassen ES, de Kam ML, Rissmann R, Groeneveld GJ. The ultraviolet B inflammation model: Postinflammatory hyperpigmentation and validation of a reduced UVB exposure paradigm for inducing hyperalgesia in healthy subjects. European Journal of Pain (United Kingdom). 2019;23(5):874-83.
Putri RS, Putra A, Chodidjah, et al. Clitorea ternatea flower extract induces platelet-derived growth factor (Pdgf) and gpx gene overexpression in ultraviolet (uv) b irradiationinduced collagen loss. Med Glas. 2023;20(1):15-21.
Chen S, He Z, Xu J. Application of adipose-derived stem cells in photoaging: basic science and literature review. Stem Cell Res Ther. 2020;11(1):1-15.
Subedi L, Lee TH, Wahedi HM, Baek SH, Kim SY. Resveratrol-Enriched Rice Attenuates UVB-ROS-Induced Skin Aging via Downregulation of Inflammatory Cascades. Oxid Med Cell Longev. 2017;2017.
Gao S, Gao S, Guo K, Chen Y, Zhao J, Jing R, et al. Keratinocyte growth factor 2 ameliorates UVB-induced skin damage via activating the AhR/nrf2 signaling pathway. Frontiers in Pharmacology. 2021; 12:655281.
Yang CY, Guo Y, Wu WJ, Man MQ, Tu Y, He L. UVB-Induced Secretion of IL-1 β Promotes Melanogenesis by Upregulating TYR/TRP-1 Expression In Vitro. Biomed Res Int. 2022; 2022(1):8230646.
Mayasari YI, Subchan P, Putra A, Chodijah C, Hussana A, Sumarawati T, et al. Secretome hypoxia mesenchymal stem cells inhibited ultraviolet radiation by inhibiting interleukin-6 through nuclear factor-kappa beta pathway in hyperpigmentation animal models. Open Access Macedonian Journal of Medical Sciences. 2023;11(B):188-94.
Munir D, Nasution IP, Restimulia L, Putra A, Amalina ND. The role of mesenchymal stem cells in allergic rhinitis and its relationship with IL-10, plasma cells and regulatory T cells. Med Glas. 2023;20(2):175-80.
Daryanti E, Putra A, Sumarawati T, Amalina ND, Prasetio A, Sidiq HA. The Comparison of Normoxic and Hypoxic Mesenchymal Stem Cells in Regulating Platelet-derived Growth Factors and Collagen Serial Levels in Skin Excision Animal Models. Open Access Maced J Med Sci. 2023;11(A):181-7.
Padhi S, Sarangi R, Ramdas A, Ravichandran K, Varghese RG, Alexander T, et al. Cutaneous hyperpigmentation in megaloblastic anemia: A five year retrospective review. Mediterranean Journal of Hematology and Infectious Diseases. 2016;8(1): e2016021.
Zhang S, Duan E. Fighting against Skin Aging: The Way from Bench to Bedside. Cell Transplant. 2018;27(5):729-738.
Dodig S, Čepelak I, Pavić I. Hallmarks of senescence and aging. Biochem Med (Zagreb). 2019;29(3):1-15.
Helfrich YR, Sachs DL, Voorhees JJ. Overview of skin aging and photoaging. Dermatology nursing / Dermatology Nurses’ Association. 2008;20(3).
Hu L, Nomura S, Sato Y, Takagi K, Ishii T, Honma Y, et al. Anti-inflammatory effects of differential molecular weight Hyaluronic acids on UVB-induced calprotectin-mediated keratinocyte inflammation. Journal of dermatological science. 2022;107(1):24-31.
Orecchioni M, Ghosheh Y, Pramod AB, Ley K. Macrophage polarization: Different gene signatures in M1(Lps+) vs. Classically and M2(LPS-) vs. Alternatively activated macrophages. Front Immunol. 2019;10(5):1-14.
Zhang QZ, Su WR, Shi SH, Wilder-Smith P, Xiang AP, Wong A, et al. Human gingiva-derived mesenchymal stem cells elicit polarization of m2 macrophages and enhance cutaneous wound healing. Stem cells. 2010;28(10):1856-68.
Horiba S, Kawamoto M, Tobita R, Kami R, Ogura Y, Hosoi J. M1/M2 Macrophage Skewing is Related to Reduction in Types I, V, and VI Collagens with Aging in Sun-Exposed Human Skin. JID Innov. 2023;3(6).
Kusumo MH, Husain SA, Amalina ND. Secretome MSCs restore α-smooth muscle actin protein tissue expression in croton oil-induced hemorrhoid rats. International Journal of Cell and Biomedical Science. 2023;2(4):139-46.
Restimulia L, Ilyas S, Munir D, Putra A, Madiadipoera T, Farhat F, et al. The CD4+ CD25+ FoxP3+ regulatory T cells regulated by MSCs suppress plasma cells in a mouse model of allergic rhinitis. Medical Archives. 2021;75(4):256.
Prajoko YW, Putra A, Dirja BT, Muhar AM, Amalina ND. The Ameliorating Effects of MSCs in Controlling Treg-mediated B-Cell Depletion by Indoleamine 2, 3-dioxygenase Induction in PBMC of SLE Patients. Open Access Maced J Med Sci. 2022;10:6-11.
Hussaana A, Suparmi, Murti HA. Protective effect of bixin isolated from Bixa orellana L. Seeds on UVB-induced inflammation and immunosuppression of the skin. Bangladesh Journal of Medical Science. 2019;18(1):107-11.
Liu YC, Zou XB, Chai YF, Yao YM. Macrophage polarization in inflammatory diseases. Int J Biol Sci. 2014;10(5):520-529.
Chen L, Tredget EE, Wu PYG, Wu Y, Wu Y. Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS One. 2008;3(4).
Lee YR, Noh EM, Han JH, Kim JM, Hwang JK, Hwang BM, et al. Brazilin inhibits UVB-induced MMP-1/3 expressions and secretions by suppressing the NF-κB pathway in human dermal fibroblasts. European Journal of Pharmacology. 2012;674(2-3):80-6.
Zukhiroh Z, Putra A, Chodidjah C, Sumarawati T, Subchan P, Trisnadi S, et al. Effect of secretome-hypoxia mesenchymal stem cells on regulating SOD and MMP-1 mRNA expressions in skin hyperpigmentation rats. Open Access Macedonian Journal of Medical Sciences. 2022;10(A):1-7.
Weiss ARR, Dahlke MH. Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of action of living, apoptotic, and dead MSCs. Front Immunol. 2019;10:1191.
He X, Dong Z, Cao Y, Wang H, Liu S, Liao L, et al. MSC‐derived exosome promotes M2 polarization and enhances cutaneous wound healing. Stem cells international. 2019;2019(1):7132708.
Darlan DM, Munir D, Putra A, Jusuf NK. MSCs-released TGFβ1 generate CD4+CD25+Foxp3+ in T-reg cells of human SLE PBMC. Journal of the Formosan Medical Association. 2021;120(1):602-8.
Liu F, Qiu H, Xue M, Zhang S, Zhang X, Xu J, et al. MSC-secreted TGF-β regulates lipopolysaccharide-stimulated macrophage M2-like polarization via the Akt/FoxO1 pathway. Stem cell research & therapy. 2019;10(1):345.
Zhao G, Liu F, Liu Z, Zuo K, Wang B, Zhang Y, et al. MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing. Stem cell research & therapy. 2020;11(1):174.
Kuntardjo N, Dharmana E, Chodidjah C, Nasihun TR, Putra A. TNF-α-Activated MSC-CM Topical Gel Effective in Increasing PDGF Level, Fibroblast Density, and Wound Healing Process Compared to Subcutaneous Injection Combination. Majalah Kedokteran Bandung. 2019;51(1):1-6.
Liang W, Chen X, Zhang S, Fang J, Chen M, Xu Y, et al. Mesenchymal stem cells as a double-edged sword in tumor growth: focusing on MSC-derived cytokines. Cellular & Molecular Biology Letters. 2021;26(1):3.
Putra A, Ridwan FB, Putridewi AI, Kustiyah AR, Wirastuti K, Sadyah NA, et al. The role of TNF-α induced MSCs on suppressive inflammation by increasing TGF-β and IL-10. Open access Macedonian journal of medical sciences. 2018;6(10):1779.
DOI: https://doi.org/10.24198/ijpst.v13i1.63650
Refbacks
- Saat ini tidak ada refbacks.
| Switch to English Back to Top |
| View My Stats Penerbit Universitas Padjadjaran
Jurnal ini terindeks di :Creative Commons Attribution :
Based on a work at http://jurnal.unpad.ac.id/ijpst/ |
Indonesian Journal of Pharmaceutical Science and Technology




