Molecular mechanisms of retinoid actions in skin

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154473/1/fsb2010009001.pd

Ultraviolet irradiation represses TGF ‐β type II receptor transcription through a 38‐bp sequence in the proximal promoter in human skin fibroblasts

Transforming growth factor‐β ( TGF ‐β) is a major regulator of collagen gene expression in human skin fibroblasts. Cellular responses to TGF ‐β are mediated primarily through its cell surface type I (TβRI) and type II (TβRII) receptors. Ultraviolet ( UV ) irradiation impairs TGF ‐β signalling largely due to reduced TβRII gene expression, thereby decreasing type I procollagen synthesis, in human skin fibroblasts. UV irradiation does not alter either TβRII m RNA or protein stability, indicating that UV reduction in TβRII expression likely results from transcriptional or translational repression. To understand how UV irradiation regulates TβRII transcription, we used a series of TβRII promoter‐luciferase 5′‐deletion constructs (covering 2 kb of the TβRII proximal promoter) to determine transcriptional rate in response to UV irradiation. We identified a 137‐bp region upstream of the transcriptional start site that exhibited high promoter activity and was repressed 60% by UV irradiation, whereas all other TβRII promoter reporter constructs exhibited either low promoter activities or no regulation by UV irradiation. Mutation of potential transcription factor binding sites within the promoter region revealed that an inverted CCAAT box (−81 bp from transcription start site) is required for promoter activity. Mutation of the CCAAT box completely abolished UV irradiation regulation of the TβRII promoter. Protein‐binding assay, as determined by electrophoretic mobility‐shift assays (EMSAs) using the inverted CCAAT box as probe (−100/−62), demonstrated significantly enhanced protein binding in response to UV irradiation. Super shift experiments indicated that nuclear factor Y ( NFY ) is able to binding to this sequence, but NFY binding was not altered in response to UV irradiation, indicating additional protein(s) are capable of binding this sequence in response to UV irradiation. Taken together, these data indicate that UV irradiation reduces TβRII expression, at least partially, through transcriptional repression. This repression is mediated by a 38‐bp sequence in TβRII promoter, in human skin fibroblasts.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108702/1/exd12389.pd

The Warty Dory, Allocyttus verrucosus, New to the Fish Fauna of Canada

In April 2010, a Warty Dory, Allocyttus verrucosus (Gilchrist, 1906), was captured during commercial fishing activities in the Labrador Sea. This is the first record for Canada and the northwest Atlantic Ocean

Age‐associated reduction of cellular spreading/mechanical force up‐regulates matrix metalloproteinase‐1 expression and collagen fibril fragmentation via c‐Jun/ AP ‐1 in human dermal fibroblasts

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109644/1/acel12265.pd

Molecular Mechanisms of Photoaging in Human Skin In Vivo and Their Prevention by All-Trans Retinoic Acid

Solar UV radiation damages human skin, affecting skin tone and resiliency and leading to premature aging (photoaging), the symptoms of which include leathery texture, wrinkles, mottled pigmentation, laxity and sallowness. We propose that photoaging results largely from UV induction of matrix metalloproteinases (MMP) that degrade skin collagen. We find that pretreatment of human skin with all- trans retinoic acid (tRA) inhibits UV induction of MMP, suggesting that tRA can protect against UV-induced collagen destruction and may therefore be able to lessen the effects of photoaging. The tRA prevents UV-induced accumulation of c-Jun protein, which is required for MMP gene expression. Activation of c-Jun transcriptional activity requires N-terminal phosphorylation. The majority of c-Jun in human skin in vivo is Nterminal phosphorylated. Topically applied t RA does not inhibit N-terminal phosphorylation by UV-induced c-Jun kinase activity in human skin. The tRA likely acts to reduce UV induction of c-Jun protein by stimulating its breakdown through the ubiquitin-proteasome pathway.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73977/1/j.1751-1097.1999.tb03268.x.pd

CYR61/CCN1: A Novel Mediator of Epidermal Hyperplasia and Inflammation in Psoriasis?

The complex pathogenesis of psoriasis is still not fully understood. The study by Sun et al. (2015) suggests that CYR61 (now named CCN1), a secreted matricellular protein, has a role in the pathogenesis of psoriasis, and thus targeting CCN1 represents a potential therapeutic strategy in its treatment

Reduced cell cohesiveness of outgrowths from eccrine sweat glands delays wound closure in elderly skin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134171/1/acel12493_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134171/2/acel12493.pd

Expression of catalytically active matrix metalloproteinase‐1 in dermal fibroblasts induces collagen fragmentation and functional alterations that resemble aged human skin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99047/1/acel12089.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99047/2/acel12089-sup-0001-FigS1-S4.pd

Laserska desorpcijsko–ionizacijska masena spektroskopija potpomognuta sa C60

An application of C60-assisted laser desorption/ionization mass spectrometry of two organic samples including insulin (5734 Da), bovine albumin (66 000 Da) and a heteropoly inorganic system: phosphotungstic acid H3PO4(WO3)12×H2O, is presented. A nitrogen laser (337 nm) on a linear tandem time-of-flight mass spectrometer is used for the observation of the laser-power dependence of mass spectra.Opisuje se primjena laserske desorpcijsko–ionizacijske masene spektroskopije sa dva organska pripravka, insulin (5734 Da) sa crijevnim albuminom (66 000 Da), te heteropolni anorganski sistem od fosforovolframske kiseline, H3PO4(WO3)12×H2O. Primijenjen je dušikov laser pri linearnom tandem masenom spektrometru s mjerenjem vremena proleta i proučavana je ovisnost masenih spektara o snazi laserskog snopa. Pokazano je da se tehnika slojeva sa C60 kao substratom za desorpciju organskih ili neorganskih molekula, može primijeniti kao alternativna dobro poznatoj MALDI metodi