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M1/M2 Macrophage Skewing is Related to Reduction in Types I, V, and VI Collagens with Aging in Sun-Exposed Human Skin 1 Introduction 1 Results 2 The M1/M2 balance is skewed in sun-exposed aged skin 2 Amount of type I collagen is related to the number of M2 macrophages in sun-exposed human skin 2 M1 (lipopolysaccharide + IFN-γ) is involved in the regulation of type I collagen production in dermal fibroblasts 3 M1 (LPS + IFN-γ) induces the expression of MMPs, and M2 (IL-4 + IL-13) induces the expression of collagen and proteins that ... 3 The amount of types V and VI collagens is related to the M1/M2 ratio in sun-exposed human skin 4 Collagen fibril formation is regulated by the M1/M2 balance of macrophages 7 Discussion 7 Materials and Methods 9 Human skin tissue 9 Histochemistry and immunofluorescence staining of human skin tissue 9 Quantification of the SHG signals in human skin tissue 11 Cell preparations 11 Ex vivo human skin model and culture 11 RNA-sequencing analysis 11 Real-time RT-PCR 11 Quantification of procollagen type I C-peptide and immunostaining of types I, V, and VI collagens 11 Statistical analysis 13 Data availability statement 13 ORCIDs 13 Conflict of Interest 13

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