Hyaluronan metabolism enhanced during epidermal differentiation is suppressed by vitamin C

Hämäläinen, Lasse; Kärkkäinen, Elisa; Takabe, Piia; Rauhala, Leena; Bart, Geneviève; Kärnä, Riikka; Pasonen‐Seppänen, Sanna; Oikari, Sanna; Tammi, Markku; Tammi, Raija

doi:10.1111/bjd.16423

Cited by 12 publications

(9 citation statements)

References 77 publications

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“…when analyzed with a competitive hyaluronan-ELSA ( Figure 1h). However, the trends were similar, and the difference is due to the ability of the competitive assay to detect smaller hyaluronan fragments (Hämäläinen et al, 2018). The amount of pericellular hyaluronan resistant to Streptomyces hyaluronidase showed an increasing trend after UVB exposure ( Figure 1f and i).…”

Section: Uvb Reduces Hyaluronan Secretion In Primary Melanocytesmentioning

confidence: 90%

Melanocyte Hyaluronan Coat Fragmentation Enhances the UVB-Induced TLR-4 Receptor Signaling and Expression of Proinflammatory Mediators IL6, IL8, CXCL1, and CXCL10 via NF-κB Activation

Takabe

Kärnä

Rauhala

et al. 2019

Journal of Investigative Dermatology

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Skin is constantly exposed to UVR, the most critical risk factor for melanoma development. Hyaluronan is abundant in the epidermal extracellular matrix and may undergo degradation by UVR. It is hypothesized that an intact hyaluronan coat around the cells protects against various agents including UVR, whereas hyaluronan fragments promote inflammation and tumorigenesis. We investigated whether hyaluronan contributes to the UVB-induced inflammatory responses in primary melanocytes. A single dose of UVB suppressed hyaluronan secretion and the expression of hyaluronan synthases HAS2 and HAS3, the hyaluronan receptor CD44, and the hyaluronidase HYAL2, as well as induced the expression of inflammatory mediators IL6, IL8, CXCL1, and CXCL10. Silencing HAS2 and CD44 partly inhibited the inflammatory response, suggesting that hyaluronan coat is involved in the process. UVB alone caused little changes in the coat, but its removal with hyaluronidase during the recovery from UVB exposure dramatically enhanced the surge of these inflammatory mediators via TLR4, p38, and NF-kB. Interestingly, exogenous hyaluronan fragments did not reproduce the inflammatory effects of hyaluronidase. We hypothesize that the hyaluronan coat on melanocytes is a sensor of tissue injury. Combined with UVB exposure, repeated injuries to the hyaluronan coat could maintain a sustained inflammatory state associated with melanomagenesis.

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Section: Uvb Reduces Hyaluronan Secretion In Primary Melanocytesmentioning

confidence: 90%

Melanocyte Hyaluronan Coat Fragmentation Enhances the UVB-Induced TLR-4 Receptor Signaling and Expression of Proinflammatory Mediators IL6, IL8, CXCL1, and CXCL10 via NF-κB Activation

Takabe

Kärnä

Rauhala

et al. 2019

Journal of Investigative Dermatology

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“…In breast cancer, disappearance of hyaluronan in some of the cancer cells correlates with high levels of nitrotyrosine, a marker of ONOOformation, suggesting ROS-induced hyaluronan fragmentation into fragments too small for histological detection [149]. Exposure to the UVradiation-induced ROS increases epidermal hyaluronan synthesis [106], while scavengers of ROS decrease the turnover of hyaluronan in epidermis [150,151]. Hyaluronan metabolism is thus closely entwined with that of ROS.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Activated hyaluronan metabolism in the tumor matrix — Causes and consequences

et al. 2019

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Hyaluronan accumulates in the stroma of several solid tumors and promotes their progression. Both enhanced synthesis and fragmentation of hyaluronan are required as a part of this inflammatory process resembling wound healing. Increased expression of the genes of hyaluronan synthases (HAS1-3) are infrequent in human tumors, while posttranslational modifications that activate the HAS enzymes, and glucose shunted to the UDP-sugar substrates HASs, can have crucial contributions to tumor hyaluronan synthesis. The pericellular hyaluronan influences virtually all cell-cell and cell-matrix interactions, controlling migration, proliferation, apoptosis, epithelial to mesenchymal transition, and stem cell functions. The catabolism by hyaluronidases and free radicals appears to be as important as synthesis for the inflammation that promotes tumor growth, since the receptors mediating the signals create specific responses to hyaluronan fragments. Targeting hyaluronan metabolism shows therapeutic efficiency in animal experiments and early clinical trials.

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“…Downregulated miR-26a-5p is also involved in barrier function of patients with atopic dermatitis [95] by targeting hyaluronan synthase 3 (HAS3), DEP domain-containing 1B (DEPDC1B), DEPDC1, nicotinamide phosphoribosyltransferase (NAMPT), DENN domain-containing 1B (DENND1B), and a disintegrin and metalloproteinase domain 19 (ADAM19), which mediate cell differentiation, cell proliferation, and anti-apoptosis. HAS catalyzes the synthesis of hyaluronan glycosaminoglycan, whose turnover in extracellular space of the vital epidermis is enhanced during epidermal differentiation [104]. Although HAS3 is one of the targets identified in downregulated miR-26a-5p [95], it is a direct target of upregulated miR-10a-5p in atopic dermatitis [12].…”

Section: Othersmentioning

confidence: 99%

The Role of MicroRNAs in Epidermal Barrier

Lee

2020

IJMS

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MicroRNAs (miRNAs), which mostly cause target gene silencing via transcriptional repression and degradation of target mRNAs, regulate a plethora of cellular activities, such as cell growth, differentiation, development, and apoptosis. In the case of skin keratinocytes, the role of miRNA in epidermal barrier integrity has been identified. Based on the impact of key genetic and environmental factors on the integrity and maintenance of skin barrier, the association of miRNAs within epidermal cell differentiation and proliferation, cell–cell adhesion, and skin lipids is reviewed. The critical role of miRNAs in the epidermal barrier extends the use of miRNAs for control of relevant skin diseases such as atopic dermatitis, ichthyoses, and psoriasis via miRNA-based technologies. Most of the relevant miRNAs have been associated with keratinocyte differentiation and proliferation. Few studies have investigated the association of miRNAs with structural proteins of corneocytes and cornified envelopes, cell–cell adhesion, and skin lipids. Further studies investigating the association between regulatory and structural components of epidermal barrier and miRNAs are needed to elucidate the role of miRNAs in epidermal barrier integrity and their clinical implications.

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Hyaluronan metabolism enhanced during epidermal differentiation is suppressed by vitamin C

Cited by 12 publications

References 77 publications

Melanocyte Hyaluronan Coat Fragmentation Enhances the UVB-Induced TLR-4 Receptor Signaling and Expression of Proinflammatory Mediators IL6, IL8, CXCL1, and CXCL10 via NF-κB Activation

Melanocyte Hyaluronan Coat Fragmentation Enhances the UVB-Induced TLR-4 Receptor Signaling and Expression of Proinflammatory Mediators IL6, IL8, CXCL1, and CXCL10 via NF-κB Activation

Activated hyaluronan metabolism in the tumor matrix — Causes and consequences

The Role of MicroRNAs in Epidermal Barrier

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