Evidence for developmentally regulated transcriptional, translational and post-translational control of metallothionein gene expression in hair follicles

1996 ◽  
Vol 8 (7) ◽  
pp. 1089 ◽  
Author(s):  
N Nishimura ◽  
GR Cam ◽  
H Nishimura ◽  
C Tohyama ◽  
Y Saitoh ◽  
...  

The distribution of metallothionein (MT) and MT mRNAs was examined in hair (wool) follicles, where high levels of cell proliferation are found and where the resulting cells provide a temporal record of differentiation events. MT was found in the cytoplasm and some nuclei of follicle bulb cells of the proliferative zone, outer root sheath cells and in basal layer cells of sebaceous glands and sweat glands. The population of 5-bromo-2'-deoxyuridine (BrdU)+ cells in these tissues overlapped, but were not completely coincident with the distribution of MT staining. MT mRNA expression in hair (wool) follicles was assessed by in situ hybridization with four gene-specific sheep MT (sMT) isoforms. Intense signals were obtained with the sMT-Ib probe in follicle bulb cells from the proliferative zone to the keratogenous zone. Signals from the sMT-Ia probe were present in the same cells, but were much weaker. No signals were detected using the sMT-Ic and sMT-II gene-specific probes. The findings suggest that: (1) MT is important in cell proliferation and/or cell differentiation in the hair follicle bulb; (2) MT translation is inhibited during cell differentiation and migration; and (3) tissue-specific expression of uncharacterized sMT isoforms is likely.

1965 ◽  
Vol 13 (8) ◽  
pp. 668-676 ◽  
Author(s):  
MICHAEL J. C. IM

The activities of the following dehydrogenase systems were demonstrated in the skin of the rhesus monkey ( Macaca mulatta): succinic, malic, isocitric (DPN and TPN), lactic, α-glycerophosphate, glucose 6-phosphate, 6-phosphogluconate, β-hydroxybutyric and glutamic dehydrogenase. Strong dehydrogenase activity in general is restricted to metabolically active sites such as the basal layer of the epidermis, the outer root sheath of the hair follicles, the hair matrix and bulb, the clear cells of the eccrine sweat glands and the basal cells of the sweat glands. The myelinated fibers of Meissner corpuscles and the inner bulb of the Pacinian corpuscles in the palms and soles abound in all of the dehydrogenases. The enzymes are also abundant in the arrectores pilorum muscles, the endothelium of the arterioles, the fibroblasts and mast cells.


2011 ◽  
Vol 22 (21) ◽  
pp. 4068-4078 ◽  
Author(s):  
Hunain Alam ◽  
Lalit Sehgal ◽  
Samrat T. Kundu ◽  
Sorab N. Dalal ◽  
Milind M. Vaidya

Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. The complex network of keratin filaments in stratified epithelia is tightly regulated during squamous cell differentiation. Keratin 14 (K14) is expressed in mitotically active basal layer cells, along with its partner keratin 5 (K5), and their expression is down-regulated as cells differentiate. Apart from the cytoprotective functions of K14, very little is known about K14 regulatory functions, since the K14 knockout mice show postnatal lethality. In this study, K14 expression was inhibited using RNA interference in cell lines derived from stratified epithelia to study the K14 functions in epithelial homeostasis. The K14 knockdown clones demonstrated substantial decreases in the levels of the K14 partner K5. These cells showed reduction in cell proliferation and delay in cell cycle progression, along with decreased phosphorylated Akt levels. K14 knockdown cells also exhibited enhanced levels of activated Notch1, involucrin, and K1. In addition, K14 knockdown AW13516 cells showed significant reduction in tumorigenicity. Our results suggest that K5 and K14 may have a role in maintenance of cell proliferation potential in the basal layer of stratified epithelia, modulating phosphatidylinositol 3-kinase/Akt–mediated cell proliferation and/or Notch1-dependent cell differentiation.


1991 ◽  
Vol 62 (8) ◽  
pp. 714-716
Author(s):  
Fumio NAKAMURA ◽  
Kunihiro KAJI ◽  
Shigeharu FUKUNAGA ◽  
Kaoru KOHNO ◽  
Keiji KONDO

1992 ◽  
Vol 12 (8) ◽  
pp. 3653-3662
Author(s):  
P Lowings ◽  
U Yavuzer ◽  
C R Goding

Melanocytes are specialized cells residing in the hair follicles, the eye, and the basal layer of the human epidermis whose primary function is the production of the pigment melanin, giving rise to skin, hair, and eye color. Melanogenesis, a process unique to melanocytes that involves the processing of tyrosine by a number of melanocyte-specific enzymes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), occurs only after differentiation from the melanocyte precursor, the melanoblast. In humans, melanogenesis is inducible by UV irradiation, with melanin being transferred from the melanocyte in the epidermis to the surrounding keratinocytes as protection from UV-induced damage. Excessive exposure to UV, however, is the primary cause of malignant melanoma, an increasingly common and highly aggressive disease. As an initial approach to understanding the regulation of melanocyte differentiation and melanocyte-specific transcription, we have isolated the gene encoding TRP-1 and examined the cis- and trans-acting factors required for cell-type-specific expression. We find that the TRP-1 promoter comprises both positive and negative regulatory elements which confer efficient expression in a TRP-1-expressing, pigmented melanoma cell line but not in NIH 3T3 or JEG3 cells and that a minimal promoter extending between -44 and +107 is sufficient for cell-type-specific expression. Assays for DNA-protein interactions coupled with extensive mutagenesis identified three factors, whose binding correlated with the function of two positive and one negative regulatory element. One of these factors, termed M-box-binding factor 1, binds to an 11-bp motif, the M box, which acts as a positive regulatory element both in TRP-1-expressing and -nonexpressing cell lines, despite being entirely conserved between the melanocyte-specific tyrosinase and TRP-1 promoters. The possible mechanisms underlying melanocyte-specific gene expression are discussed.


1993 ◽  
Vol 13 (6) ◽  
pp. 3176-3190
Author(s):  
C Byrne ◽  
E Fuchs

Keratins K5 and K14 form the extensive intermediate filament network of mitotically active basal cells in all stratified epithelia. We have explored the regulatory mechanisms governing cell-type-specific and differentiation stage-specific expression of the human K5 gene in transiently transfected keratinocytes in vitro and in transgenic mice in vivo. Six thousand base pairs of 5' upstream K5 sequence directed proper basal cell-specific expression in all stratified epithelia. Surprisingly, as few as 90 bp of the K5 promoter still directed expression to stratified epithelia, with expression predominantly in epidermis, hair follicles, and tongue. Despite keratinocyte-preferred expression, the truncated K5 promoter displayed departures from basal to suprabasal expression in epidermis and from outer root sheath to inner root sheath expression in the follicle, with some regional variations in expression as well. To begin to elucidate the molecular controls underlying the keratinocyte specificity of the truncated promoter, we examined protein-DNA interactions within this region. A number of keratinocyte nuclear proteins bind to a K5 gene segment extending from -90 to +32 bp and are functionally involved in transcriptional regulation in vitro. Interestingly, several of these factors are common to both the K5 and K14 promoters, although they appear to be distinct from those previously implicated in keratinocyte specificity. Mutagenesis studies indicate that factors binding in the vicinity of the TATA box and transcription initiation are responsible for the cell type specificity of the truncated K5 promoter.


1992 ◽  
Vol 12 (8) ◽  
pp. 3653-3662 ◽  
Author(s):  
P Lowings ◽  
U Yavuzer ◽  
C R Goding

Melanocytes are specialized cells residing in the hair follicles, the eye, and the basal layer of the human epidermis whose primary function is the production of the pigment melanin, giving rise to skin, hair, and eye color. Melanogenesis, a process unique to melanocytes that involves the processing of tyrosine by a number of melanocyte-specific enzymes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), occurs only after differentiation from the melanocyte precursor, the melanoblast. In humans, melanogenesis is inducible by UV irradiation, with melanin being transferred from the melanocyte in the epidermis to the surrounding keratinocytes as protection from UV-induced damage. Excessive exposure to UV, however, is the primary cause of malignant melanoma, an increasingly common and highly aggressive disease. As an initial approach to understanding the regulation of melanocyte differentiation and melanocyte-specific transcription, we have isolated the gene encoding TRP-1 and examined the cis- and trans-acting factors required for cell-type-specific expression. We find that the TRP-1 promoter comprises both positive and negative regulatory elements which confer efficient expression in a TRP-1-expressing, pigmented melanoma cell line but not in NIH 3T3 or JEG3 cells and that a minimal promoter extending between -44 and +107 is sufficient for cell-type-specific expression. Assays for DNA-protein interactions coupled with extensive mutagenesis identified three factors, whose binding correlated with the function of two positive and one negative regulatory element. One of these factors, termed M-box-binding factor 1, binds to an 11-bp motif, the M box, which acts as a positive regulatory element both in TRP-1-expressing and -nonexpressing cell lines, despite being entirely conserved between the melanocyte-specific tyrosinase and TRP-1 promoters. The possible mechanisms underlying melanocyte-specific gene expression are discussed.


2019 ◽  
Vol 19 (1S) ◽  
pp. 22-24 ◽  
Author(s):  
E A Guryanova ◽  
E S Deomidov

Objective. We studied mast cells and neuroendocrine cells of the skin of adults in the area of the acupuncture points (AP) and outside them. Material and methods. Using the Unna method (polychrome toluidine blue dye), mast cells were detected in the skin. Conducted immunohistochemical study using monoclonal antibodies to neuron-specific enolase and synaptophysin in order to identify neuroendocrine cells. Research results. Analyzed data on the distribution of mast cells in the skin in the area of the acupuncture points in an adult. It was revealed that the distribution of mast cells in the dermis and the hypodermis differs depending on the localization of the acupuncture point. Fat cells take in maintaining homeostasis and regulation of metabolism in the skin. NSE- and synaptophysin-positive cells were detected in the basal layer of the epidermis, in the area of the the muscles that raise the hair, in the area of the hair follicles; in the secretory terminal regions of the sweat glands, as well as outwards from the basement membrane of these regions between the myoepithelial cells. A part of the neuroendocrine cells is in contact with nerve waves. Expression of NSE and synaptophysin depends on AP localization. In AP of the skin of the abdomen and upper limb, a more pronounced expression of NSE and synaptophysin is observed than at the acupuncture points of the skin of the face. The expression of NSE in the structures of the skin in the area of the acupuncture points is more pronounced than the expression of synaptophysin. In the dermis revealed structureless spaces surrounded by mast cells, nerve fibers, blood vessels.


1957 ◽  
Vol 3 (3) ◽  
pp. 343-348 ◽  
Author(s):  
William Montagna

1. Various amounts of ß-glucuronidase activity may be found in all of the cutaneous appendages. 2. In the epidermis, the basal layer and the Malpighian layer contain a moderate amount of it, but a band of cells, including the stratum granulosum and the cells immediately above it, is rich in ß-glucuronidase. 3. The cells of the duct of eccrine sweat glands have moderately strong enzyme activity, but those in the secretory coil are strongly reactive; small and large reactive granules are crowded in the reactive cytoplasm. 4. The cells of the secretory coil of the apocrine glands contain more ß-glucuronidase than any other cutaneous appendage. 5. In the sebaceous glands, a very strong concentration of enzyme activity is found in the undifferentiated peripheral cells, a smaller amount of it is found in the differentiating cells. 6. In active hair follicles, the largest amount of ß-glucuronidase is found in the outer root sheath and in the bulb. In the outer sheath, the strongest concentration is found around the level of the keratogenous zone of the cortex. The dermal papilla is strongly reactive. In quiescent hair follicles, the outer root sheath has a moderate amount of enzyme concentration, but the dermal papilla is unreactive. 7. In the dermis, the fibroblasts in the papillary layer, the smooth muscle cells of the arrectores pilorum and the tunica media of arteries, and the fat cells all exhibit enzyme activity. Mast cells show a great concentration of ß-glucuronidase.


1994 ◽  
Vol 126 (2) ◽  
pp. 495-506 ◽  
Author(s):  
H Tseng ◽  
H Green

Basonuclin is a protein possessing three pairs of zinc fingers and a nuclear localization signal. Expression of the gene is largely confined to keratinocytes of stratified squamous epithelia and hair follicles. In the epidermis and in stratified epidermal cultures, basonuclin is present in the nuclei of cells in or close to the basal layer but not in the nuclei of cells in more superficial layers. The Ki-67 protein, a nuclear marker for any stage of the multiplication cycle is present in only a subclass of basonuclin-containing cells. In cultured keratinocytes, the disappearance of basonuclin mRNA is associated with loss of colony-forming ability and the appearance of mRNA for involucrin, a protein characteristic of terminal differentiation. In hair follicles, the largest reservoir of basonuclin-containing cells is the outer root sheath, which contains precursors of differentiated cells of the hair shaft and of the epidermis. Basonuclin is not a cell cycle marker but is likely instead to be a regulatory molecular whose presence in the keratinocyte is linked to the maintenance of proliferative capacity and prevention of terminal differentiation.


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