“…Staining with Oil Red O to identify lipids revealed subcutaneous adipose tissue in both control and K5-Gli2⌬C4 skin, but sebaceous glands were conspicuously absent in the transgenic skin samples ( Figure 1, C and D). Extensive sebaceous gland development normally occurs during the perinatal period, reflected by the accumulation of transcripts encoding the sebocyte markers Scd3 28 and Mc5r 32 between day 1 and 9 in control skin ( Figure 1E). In skin from 9-day-old K5-Gli2⌬C4 mice, however, Scd3 mRNA was nearly undetectable and Mc5r transcripts were present at levels comparable to day 1.…”
Section: Resultsmentioning
confidence: 99%
“…Primers were selected to span an intron whenever possible, or PCR was performed in the absence of reverse transcriptase to rule out the possibility that amplification products were derived from contaminating DNA. PCR conditions are available on request; the following primers were used: actin (421 bp) forward 5Ј-TACCACAGGCATTGTGAT-GGA-3Ј, reverse 5Ј-CAACGTCACACTTCATGATGG-3Ј 27 ; c-Myc (548 bp) forward 5Ј-AGTGCATTGATCCCTCAGT-GGTCTTTCCCTA-3Ј, reverse 5Ј-CAGCTCGTTCCTCC-TCTGACGTTCCAAGACGTT-3Ј; Gli1 (364 bp) forward 5Ј-GTCGGAAGTCCTATTCACGC-3Ј, reverse 5Ј-CAGT-CTGCTCTCTTCCCTGC-3Ј; M2SMO (435 bp) forward 5Ј-AAGCGGATCAAGAAGAGCA-3Ј, reverse 5Ј-GAG-GCAGTCGAGGAATGGTA-3Ј; Mc5r (490 bp) forward 5Ј-AAATCCGATGCCAAGAAGTG-3Ј, reverse 5Ј-GG-TAGCGCAAGGCATAGAAG-3Ј; Scd3 (809 bp) forward 5Ј-CTTGGATAACCACCCTGGGTG-3Ј, reverse 5Ј-CTC-CTCTGGAACATCACCAGCTTC-3Ј; 28 Shh (241 bp) forward 5Ј-TCTGTGATGAACCAGTGGCC-3Ј, reverse 5Ј-GCCACGGAGTTCTCTGCTTT-3Ј. 29 …”
Epithelial progenitor cells in skin give rise to multiple lineages, comprising the hair follicle, an associated sebaceous gland, and overlying epidermis; however, the signals that regulate sebocyte development are poorly understood. We tested the potential involvement of the Hedgehog pathway in sebaceous gland development using transgenes designed to either block or stimulate Hedgehog signaling in cutaneous keratinocytes in vivo. Whereas inhibition of the Hedgehog pathway selectively suppressed sebocyte development, Hedgehog pathway activation led to a striking increase both in size and number of sebaceous glands. Remarkably, ectopic Hedgehog signaling also triggered the formation of sebaceous glands from footpad epidermis, in regions normally devoid of hair follicles and associated structures. These ectopic sebaceous glands expressed molecular markers of sebocyte differentiation and were functional, secreting their contents directly onto the skin's surface instead of into a hair canal. The Hedgehog pathway thus plays a key role in sebocyte cell fate decisions and is a potential target for treatment of skin disorders linked to abnormal sebaceous gland function, such as acne.
“…Staining with Oil Red O to identify lipids revealed subcutaneous adipose tissue in both control and K5-Gli2⌬C4 skin, but sebaceous glands were conspicuously absent in the transgenic skin samples ( Figure 1, C and D). Extensive sebaceous gland development normally occurs during the perinatal period, reflected by the accumulation of transcripts encoding the sebocyte markers Scd3 28 and Mc5r 32 between day 1 and 9 in control skin ( Figure 1E). In skin from 9-day-old K5-Gli2⌬C4 mice, however, Scd3 mRNA was nearly undetectable and Mc5r transcripts were present at levels comparable to day 1.…”
Section: Resultsmentioning
confidence: 99%
“…Primers were selected to span an intron whenever possible, or PCR was performed in the absence of reverse transcriptase to rule out the possibility that amplification products were derived from contaminating DNA. PCR conditions are available on request; the following primers were used: actin (421 bp) forward 5Ј-TACCACAGGCATTGTGAT-GGA-3Ј, reverse 5Ј-CAACGTCACACTTCATGATGG-3Ј 27 ; c-Myc (548 bp) forward 5Ј-AGTGCATTGATCCCTCAGT-GGTCTTTCCCTA-3Ј, reverse 5Ј-CAGCTCGTTCCTCC-TCTGACGTTCCAAGACGTT-3Ј; Gli1 (364 bp) forward 5Ј-GTCGGAAGTCCTATTCACGC-3Ј, reverse 5Ј-CAGT-CTGCTCTCTTCCCTGC-3Ј; M2SMO (435 bp) forward 5Ј-AAGCGGATCAAGAAGAGCA-3Ј, reverse 5Ј-GAG-GCAGTCGAGGAATGGTA-3Ј; Mc5r (490 bp) forward 5Ј-AAATCCGATGCCAAGAAGTG-3Ј, reverse 5Ј-GG-TAGCGCAAGGCATAGAAG-3Ј; Scd3 (809 bp) forward 5Ј-CTTGGATAACCACCCTGGGTG-3Ј, reverse 5Ј-CTC-CTCTGGAACATCACCAGCTTC-3Ј; 28 Shh (241 bp) forward 5Ј-TCTGTGATGAACCAGTGGCC-3Ј, reverse 5Ј-GCCACGGAGTTCTCTGCTTT-3Ј. 29 …”
Epithelial progenitor cells in skin give rise to multiple lineages, comprising the hair follicle, an associated sebaceous gland, and overlying epidermis; however, the signals that regulate sebocyte development are poorly understood. We tested the potential involvement of the Hedgehog pathway in sebaceous gland development using transgenes designed to either block or stimulate Hedgehog signaling in cutaneous keratinocytes in vivo. Whereas inhibition of the Hedgehog pathway selectively suppressed sebocyte development, Hedgehog pathway activation led to a striking increase both in size and number of sebaceous glands. Remarkably, ectopic Hedgehog signaling also triggered the formation of sebaceous glands from footpad epidermis, in regions normally devoid of hair follicles and associated structures. These ectopic sebaceous glands expressed molecular markers of sebocyte differentiation and were functional, secreting their contents directly onto the skin's surface instead of into a hair canal. The Hedgehog pathway thus plays a key role in sebocyte cell fate decisions and is a potential target for treatment of skin disorders linked to abnormal sebaceous gland function, such as acne.
“…Four SCD isoforms (Scd1-Scd4) have been identified in the mouse, which reside within a 200 kb region of mouse chromosome 19 [6][7][8][9][10]. Scd1 and Scd2 expression is observed in a variety of lipogenic tissues, including liver and adipose tissue, Scd3 is primarily expressed in the skin, Harderian gland and preputial gland, and Scd4 is mainly expressed in the heart [5,6,9].…”
Section: Multiple Isoforms Of Mouse and Human Scdmentioning
confidence: 99%
“…Scd1 and Scd2 expression is observed in a variety of lipogenic tissues, including liver and adipose tissue, Scd3 is primarily expressed in the skin, Harderian gland and preputial gland, and Scd4 is mainly expressed in the heart [5,6,9]. SCD3 is a palmitoyl-CoA desaturase with minimal desaturase activity towards stearoyl-CoA, while SCD1, SCD2, and SCD4 desaturate both palmitoyl-CoA and stearoylCoA to palmitoleoyl-CoA and oleoyl-CoA, respectively [11].…”
Section: Multiple Isoforms Of Mouse and Human Scdmentioning
confidence: 99%
“…The skin expresses three isoforms of SCD, Scd1-Scd3 [6,12,41]. In adult mice, Scd1 is found in presebocytes and Scd3 in mature sebocytes [6].…”
Section: Importance Of Scd For Skin Biology and Developmentmentioning
Purpose of review-Stearoyl-coenzyme A desaturase 1 is a δ-9 fatty acid desaturase that catalyzes the synthesis of monounsaturated fatty acids and has emerged as a key regulator of metabolism. This review evaluates the latest advances in our understanding of the pivotal role of stearoyl-coenzyme A desaturase 1 in health and disease.Recent findings-scd1-deficient mice have reduced lipid synthesis and enhanced lipid oxidation, thermogenesis and insulin sensitivity in various tissues including liver, muscle and adipose tissue due to transcriptional and posttranscriptional effects. These metabolic changes protect scd1-deficient mice from a variety of dietary, pharmacological and genetic conditions that promote obesity, insulin resistance and hepatic steatosis. Stearoylcoenzyme A desaturase 1 is required to guard against dietary unsaturated fat deficiency, leptin deficiency-induced diabetes, and palmitate-induced lipotoxic insults in muscle and pancreatic β-cells. Paradoxical observations of increased muscle stearoyl-coenzyme A desaturase 1 during obesity, starvation and exercise raise questions as to the role of stearoyl-coenzyme A desaturase 1 in this tissue. Mice with a liverspecific loss of stearoyl-coenzyme A desaturase 1, and inhibition of stearoyl-coenzyme A desaturase 1 via antisense or RNA interference, recapitulate only a subset of the phenotypes observed in global Scd1 deficiency, indicating the involvement of multiple tissues.Summary-Recent studies in humans and animal models have highlighted that modulation of stearoyl-coenzyme A desaturase 1 activity by dietary intervention or genetic manipulation strongly influences several facets of energy metabolism to affect susceptibility to obesity, insulin resistance, diabetes and hyperlipidemia.
Mammailan stearyol‐CoA desaturase (SCD) is a membrane embedded protein that introduces a double bond into a saturated fatty acid. Humans have two homologs (SCD1 and 5) and mice have four (SCD1–4). The functions of SCD have been studied for over 40 years, and recently crystal structures of human and mouse SCD1 have been reported. Here we review the structure and function of SCD.
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