The Role of Integrins in the Development and Homeostasis of the Epidermis and Skin Appendages

Integrins play a critical role in the regulation of adhesion, migration, proliferation, and differentiation of cells. Because of the variety of the functions they play in the cell, they are necessary for the formation and maintenance of tissue structure integrity. The trove of data accumulated by researchers suggests that integrins participate in the morphogenesis of the epidermis and its appendages. The development of mice with tissue-specific integrin genes knockout and determination of the genetic basis for a number of skin diseases in humans showed the significance of integrins in the biology, physiology, and morphogenesis of the epidermis and hair follicles. This review discusses the data on the role of different classes of integrin receptors in the biology of epidermal cells, as well as the development of the epidermis and hair follicles.

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Critical role of WNK1 in MYC-dependent early mouse thymocyte development

eLife ◽

10.7554/elife.56934 ◽

2020 ◽

Vol 9 ◽

Author(s):

Robert Köchl ◽

Lesley Vanes ◽

Miriam Llorian Sopena ◽

Probir Chakravarty ◽

Harald Hartweger ◽

...

Keyword(s):

Critical Role ◽

Ion Homeostasis ◽

Thymocyte Development ◽

Double Positive ◽

Mouse Thymocyte ◽

Proliferation And Differentiation ◽

Tcr Signals ◽

And Migration ◽

Early Mouse

WNK1, a kinase that controls kidney salt homeostasis, also regulates adhesion and migration in CD4+ T cells. Wnk1 is highly expressed in thymocytes, and since migration is important for thymocyte maturation, we investigated a role for WNK1 in mouse thymocyte development. We find that WNK1 is required for the transition of double negative (DN) thymocytes through the β-selection checkpoint and subsequent proliferation and differentiation into double positive (DP) thymocytes. Furthermore, we show that WNK1 negatively regulates LFA1-mediated adhesion and positively regulates CXCL12-induced migration in DN thymocytes. Despite this, migration defects of WNK1-deficient thymocytes do not account for the developmental arrest. Instead, we show that in DN thymocytes WNK1 transduces pre-TCR signals via OXSR1 and STK39 kinases, and the SLC12A2 ion co-transporter that are required for post-transcriptional upregulation of MYC and subsequent proliferation and differentiation into DP thymocytes. Thus, a pathway regulating ion homeostasis is a critical regulator of thymocyte development.

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Leptin System in Obese Dog Skin: A Pilot Study

Animals ◽

10.3390/ani10122338 ◽

2020 ◽

Vol 10 (12) ◽

pp. 2338

Author(s):

Margherita Maranesi ◽

Antonio Di Loria ◽

Cecilia Dall’Aglio ◽

Diego Piantedosi ◽

Elvio Lepri ◽

...

Keyword(s):

Immune System ◽

Skin Diseases ◽

Skin Inflammation ◽

Normal Weight ◽

Hair Follicles ◽

Obese Group ◽

System Control ◽

System Composition ◽

Skin Biology

Obesity predisposes to several health problems including skin diseases. However, information on the relationship between obesity and skin disorders in pets is very scarce. Leptin (LEP) is mainly produced by adipose tissue and has a prominent role in skin biology. This study evaluated the LEP system in the skin of obese dogs compared to normal-weight animals. The investigation was carried out on 10 obese (Obese group) and 10 normal-weight (Normal-weight group) dogs through Real-time PCR and immunohistochemistry. Cells of skin associated immune system were also evaluated. No differences were evidenced between the two groups as well as skin inflammation. LEP differences were no significant, while LEPR transcript appeared 10-fold higher in obesedogs than in normal-weight ones. Immunostaining for both molecules was observed in several skin structures such as the epidermis, hair follicles, and glands. No differences appeared in the skin associated immune system composition. This study is a preliminary report showing that LEP system changes in obese dog skin. The increased LEPR expression observed in the obese group suggests that the receptor plays a modulating role in the system control. However, the exact role of LEPin the skin under obesity conditions needs further elucidation.

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Critical role of integrin CD11c in splenic dendritic cell capture of missing-self CD47 cells to induce adaptive immunity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1805542115 ◽

2018 ◽

Vol 115 (26) ◽

pp. 6786-6791 ◽

Cited By ~ 15

Author(s):

Jiaxi Wu ◽

Huaizhu Wu ◽

Jinping An ◽

Christie M. Ballantyne ◽

Jason G. Cyster

Keyword(s):

Critical Role ◽

T Cell Proliferation ◽

Cell Capture ◽

Antigen Uptake ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Missing Self

CD11c, also known as integrin alpha X, is the most widely used defining marker for dendritic cells (DCs). CD11c can bind complement iC3b and mediate phagocytosis in vitro, for which it is also referred to as complement receptor 4. However, the functions of this prominent marker protein in DCs, especially in vivo, remain poorly defined. Here, in the process of studying DC activation and immune responses induced by cells lacking self-CD47, we found that DC capture of CD47-deficient cells and DC activation was dependent on the integrin-signaling adaptor Talin1. Specifically, CD11c and its partner Itgb2 were required for DC capture of CD47-deficient cells. CD11b was not necessary for this process but could partially compensate in the absence of CD11c. Mice with DCs lacking Talin1, Itgb2, or CD11c were defective in supporting T-cell proliferation and differentiation induced by CD47-deficient cell associated antigen. These findings establish a critical role for CD11c in DC antigen uptake and activation in vivo. They may also contribute to understanding the functional mechanism of CD47-blockade therapies.

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Polymorphisms in Genes Involved in Steroidogenesis in the Development of Severe Acne

International Journal of Biomedicine ◽

10.21103/article11(3)_oa4 ◽

2021 ◽

Vol 11 (3) ◽

pp. 275-280

Author(s):

Alexander G. Rumyantsev ◽

Olga M. Dеmina

Keyword(s):

Molecular Genetic ◽

Hair Follicles ◽

Genetic Diagnostics ◽

Control Group ◽

Severe Acne ◽

High Throughput Dna Sequencing ◽

Molecular Genetic Diagnostics ◽

Gene 4

Background: Acne is a multifactorial disease, in the pathogenesis of which one of the leading factors is the excessive effect of androgens on the hair follicles (HFs) and sebaceous glands (SGs), along with hypersecretion of sebum, pathological follicular hyperkeratosis and an inflammatory response. The search for genotypic markers in patients with varying severity of acne is a difficult task due to the multifactorial pathogenesis and the role of trigger factors in the formation of acne. The aim of this study was to determine SNPs within 3 genes involved in steroidogenesis (MVK, ARPC1B, and CA2) in patients with severe acne. Methods and Results: The study included 70 patients (42 men and 28 women) aged between 15 and 46 years (the median age - 22.1 years). The main group (MG) included 50 patients (29 men and 21 women) with severe acne. The control group (CG) consisted of 20 apparently healthy individuals (13 men and 7 women). Molecular-genetic diagnostics was carried out by the method of high-throughput DNA sequencing (next-generation sequencing). Our study showed that severe acne is associated with 12 polymorphic loci of the MVK gene (4 SNPs in exons and 8 SNPs in introns), 7 SNPs of the ARPC1B gene (2 SNPs in exons and 5 SNPs in introns), and 9 SNPs of the CA2 gene (3 SNPs in exons and 6 SNPs in introns). Conclusion: The revealed features of the SNPs within the MVK, ARPC1B, and CA2 genes in patients with severe acne probably indicate a hereditary determination of steroidogenesis in acne.

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ROLE OF DERMATOSCOPY IN CHRONIC DERMATOSES DIAGNOSIS

International Medical Journal ◽

10.37436/2308-5274-2020-2-11 ◽

2020 ◽

pp. 53-56

Author(s):

G. S. Chekhovska

Keyword(s):

Differential Diagnosis ◽

Lupus Erythematosus ◽

Skin Diseases ◽

Seborrheic Dermatitis ◽

Hair Follicles ◽

Discoid Lupus Erythematosus ◽

Non Invasive ◽

Invasive Method ◽

Vascular Structures

Dermatoscopy is a valuable auxiliary non−invasive method used in the diagnosis of inflammatory, parasitic and viral skin diseases. Treatment of dermatoses is based on the results of analysis of melanin, follicular−horny and vascular components. Diagnosis begins with polarized dermatoscopy and then progresses to non−polarized using immersion fluid. At dermatoscopic inspection of a psoriatic plaque the point vessels evenly distributed along all the surface (a symptom of "scattered red pepper") are noted. Eczema is characterized by focal accumulation of blood vessels in the form of dots, peeling, yellowish crusts. Examination of discoid lupus erythematosus foci often reveals individual linear or branched vessels, their location is random. Red herpes zoster is dermatoscopically characterized by vascular structures in the form of large granular horny plugs of whitish color with a pearly sheen. The most informative is dermatoscopy in the differential diagnosis of erythematous form of rosacea and seborrheic dermatitis. On the erythematous background, dilated vessels around the sebaceous hair follicles, large vascular polygons formed from vessels thicker than in healthy skin and seborrheic dermatitis are found. At inspection of the fresh centers of a sclero−atrophic lichen diffuse unstructured zones of white color with a peripheral erythematous corolla and with numerous light comedic structures on a surface are visualized. At dermatoscopy of the Little − Lassueur syndrome in follicular papules on skin gray, violet points located in the form of a circle are noted. Dermatoscopy is increasingly used in dermatology, especially in the differential diagnosis of dermatoses of inflammatory and parasitic nature.

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MicroRNA-19b-3p promotes cell proliferation and osteogenic differentiation of BMSCs by interacting with lncRNA H19

BMC Medical Genetics ◽

10.1186/s12881-020-0948-y ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 2

Author(s):

Gan Xiaoling ◽

Liu Shuaibin ◽

Liang Kailu

Keyword(s):

Cell Proliferation ◽

Protein Expression ◽

Postmenopausal Osteoporosis ◽

Critical Role ◽

Dependent Manner ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

17Β Estradiol ◽

Dose Dependent

Abstract Background To investigated the role of miR-19b-3p in regulating bone marrow mesenchymal stem cell (BMSC) proliferation and osteoblast differentiation. Methods The expression of miR-19b-3p and lncRNA H19 were measured in postmenopausal osteoporosis patients and BMP-22 induced BMSCs using qRT-PCR. MiR-19b-3p mimic or inhibitor was transfected into BMP-2 induced BMSCs. Cell proliferation was measured by BrdU method. Protein expression of RUNX2 and COL1A1 were measured by western blot. PcDNA3.1-lncRNA H19 with or without miR-19b-3p mimic was transfected into BMP-2 induced BMSCs. Results The expression of miR-19b-3p was significantly up-regulated in postmenopausal osteoporosis patients and BMP-2 induced BMSCs. MiR-19b-3p overexpression dramatically elevated, while miR-19b-3p inhibition decreased cell proliferation of BMSCs. Additionally, protein expression levels of RUNX2 and COL1A1, as well as ALP activity were significantly promoted by miR-19b-3p mimic transfection and inhibited by miR-19b-3p inhibitor transfection. LncRNA H19 was obviously down-regulated in postmenopausal osteoporosis patients. H19 overexpression significantly decreased cell proliferation and differentiation by down-regulating miR-19b-3p. Moreover, the expression of miR-19b-3p was inhibited, while H19 elvated in 17β-estradiol (E2) treated BMSCs in a dose-dependent manner. Conclusion These data were the first to reveal the critical role of H19/miR-19b-3p in postmenopausal osteoporosis, and provided a new therapeutic target for OP.

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Incorporation of DNA methylation into eQTL mapping in African Americans

10.1101/2020.08.05.238030 ◽

2020 ◽

Author(s):

Anmol Singh ◽

Yizhen Zhong ◽

Layan Nahlawi ◽

C. Sehwan Park ◽

Tanima De ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

African Americans ◽

Genetic Basis ◽

Critical Role ◽

Eqtl Analysis ◽

Biliary Cirrhosis ◽

Eqtl Mapping ◽

Genome Wide

Epigenetics is a reversible molecular mechanism that plays a critical role in many developmental, adaptive, and disease processes. DNA methylation has been shown to regulate gene expression and the advent of high throughput technologies has made genome-wide DNA methylation analysis possible. We investigated the effect of DNA methylation in eQTL mapping (methylation-adjusted eQTLs), by incorporating DNA methylation as a SNP-based covariate in eQTL mapping in African American derived hepatocytes. We found that the addition of DNA methylation uncovered new eQTLs and eGenes. Previously discovered eQTLs were significantly altered by the addition of DNA methylation data suggesting that methylation may modulate the association of SNPs to gene expression. We found that methylation-adjusted eQTLs which were less significant compared to PC-adjusted eQTLs were enriched in lipoprotein measurements (FDR = 0.0040), immune system disorders (FDR = 0.0042), and liver enzyme measurements (FDR = 0.047), suggesting a role of DNA methylation in regulating the genetic basis of these phenotypes. Our methylation-adjusted eQTL analysis also uncovered novel SNP-gene pairs. For example, our study found the SNP, rs11546996, was associated to PNKP. In a previous GWAS, this SNP was associated with primary biliary cirrhosis although the causal gene was thought to be SPIB. Our methylation-adjusted method potentially adds new understanding to the genetic basis of complex diseases that disproportionally affect African Americans.

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MicroRNA Profiling Reveals an Abundant ssc-miRNA-148a-3p that Promotes Proliferation and Differentiation during Intramuscular Adipogenesis in Chinese Guizhou Congjiang Pigs Breeds by targeting PPARGC1A

10.21203/rs.3.rs-818015/v1 ◽

2021 ◽

Author(s):

Lulin Tan ◽

Zhaojun Chen ◽

Mingde Teng ◽

Bin Chen ◽

Houqiang Xu

Keyword(s):

Expression Profiles ◽

Critical Role ◽

Differentially Expressed ◽

Marker Genes ◽

Preadipocyte Differentiation ◽

Longissimus Dorsi Muscle ◽

Non Coding Rna ◽

Proliferation And Differentiation ◽

G2 Phase

Abstract BackgroundIntramuscular fat development is regulated by a series of complicated processes, and non-coding RNA (ncRNA) such as microRNA (miRNA) plays a critical role during intramuscular preadipocyte proliferation and differentiation development in pigs. In present research, we detected the expression profiles of miRNA during different differentiation stages, namely, day 0 (D0), day 4 (D4), and day 8 (D8), of intramuscular preadipocytes from the longissimus dorsi muscle of Chinese Guizhou Congjiang pigs to provide first insights into their potential involvement in intramuscular preadipocyte development. And we investigated the function of miR-148a-3p in adipocyte proliferation, apoptosis, and differentiation. ResultsA total of 67, 95, and 16 differentially expressed (DE) miRNAs were detected between D4 and D0, between D8 and D0, and between D8 and D4, respectively. We further characterized the role of miR-148a-3p which was differentially expressed and highest expressed abundance in D0, D4, and D8. To explore the role of miR-148a-3p in porcine intramuscular preadipocyte, miR-148a-3p mimics and inhibitors were used to perform miR-148a-3p overexpression and knockdown, respectively. Overexpression of miRNA-148a-3p increased the number of intramuscular preadipocytes in the S/G2 phase of the cell cycle and decreased the proportion of cells in the G0/G1 phase. Moreover, it promoted proliferation by regulation of cyclin B, cyclin G1, cyclin D1, CDK2, CDK3, and CDK4 and inhibited apoptosis of intramuscular preadipocyte by regulating the expression of Caspase-3, Bax, and Bcl-2. Meanwhile, the mimics of miR-148a-3p dramatically promoted intramuscular preadipocyte differentiation and upregulated the expression levels of adipogenic marker genes PPARγ, FASN, FABP4, HSL, APOE, LPL, and CEBPα. Furthermore, miR-148a-3p promoted intramuscular preadipocyte differentiation via restraining the AMPK/ACC/CPT1C signaling pathway. PPARGC1A was identified as a target gene of miR-148a-3p by luciferase activity and western blotting assays. ConclusionOur study provides novel insights into the regulatory mechanisms underlying intramuscular preadipocyte development and identified amount of miRNAs whose regulatory potential will need to be explored in the future. Our results establish that miR-148a-3p promoted adipocyte differentiation by targeting PPARGC1A.

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Determination of Cell Function in an Insect

Development ◽

10.1242/dev.1.3.269 ◽

1953 ◽

Vol 1 (3) ◽

pp. 269-277

Author(s):

V. B. Wigglesworth

Keyword(s):

Cell Function ◽

Single Layer ◽

Rhodnius Prolixus ◽

Epidermal Cells ◽

The Body ◽

Dermal Glands ◽

Clear Space

I Propose to consider two kinds of determination and differentiation which have been studied in the hemipteron Rhodnius prolixus. (i) The determination of the cell or group of cells, with their subsequent differentiation to produce a given part of the body, (ii) The determination or control of the characters of that part—whether these are to be juvenile (larval) or adult (imaginal). Discussion of this second type of determination will require consideration of the role of hormones in controlling differentiation in insects. The integument of the abdomen in the Rhodnius larva consists of a single layer of epidermal cells and the overlying cuticle. At regular intervals the cuticle is modified to form little plaques each of which bears an innervated bristle (Wigglesworth, 1933). The cuticle is pierced at intervals by the ducts of dermal glands: these form a cluster of 4 or 5 around each plaque, with occasional single glands in the clear space between (Wigglesworth, 1947) (Fig. 3, A).

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Mechanical strain enhances survivability of collagen micronetworks in the presence of collagenase: implications for load-bearing matrix growth and stability

Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rsta.2009.0093 ◽

2009 ◽

Vol 367 (1902) ◽

pp. 3339-3362 ◽

Cited By ~ 80

Author(s):

Amit P. Bhole ◽

Brendan P. Flynn ◽

Melody Liles ◽

Nima Saeidi ◽

Charles A. Dimarzio ◽

...

Keyword(s):

Critical Role ◽

Mechanical Strain ◽

Material System ◽

Contrast Imaging ◽

Load Bearing ◽

Collagenous Tissue ◽

Collagen Molecules ◽

Fibroblastic Cells

There has been great interest in understanding the methods by which collagen-based load-bearing tissue is constructed, grown and maintained in vertebrate animals. To date, the responsibility for this process has largely been placed with mesenchymal fibroblastic cells that are thought to fully control the morphology of load-bearing extracellular matrix (ECM). However, given clear limitations in the ability of fibroblastic cells to precisely place or remove single collagen molecules to sculpt tissue, we have hypothesized that the material itself must play a critical role in the determination of the form of structural ECM. We here demonstrate directly, using live, dynamic, differential interference contrast imaging, that mechanically strained networks of collagen fibrils, exposed to collagenase ( Clostridium histolyticum ), degrade preferentially. Specifically, unstrained fibrils are removed ‘quickly’, while strained fibrils persist significantly longer. The demonstration supports the idea that collagen networks are mechanosensitive in that they are stabilized by mechanical strain. Thus, collagen molecules (together with their complement enzymes) may comprise the basis of a smart, load-adaptive, structural material system. This concept has the potential to drastically simplify the assumed role of the fibroblast, which would need only to provide ECM molecules and mechanical force to sculpt collagenous tissue.

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