Tropomyosin-receptor kinase fused gene (TFG) regulates lipid production in human sebocytes

Choi, So Ra; Hwang, Yul Lye; Kim, Soo Jung; Sohn, Kyung Cheol; Choi, Chong Won; Park, Kyung Duck; Lee, Young; Seo, Young Joon; Lee, Jeung Hoon; Hong, Soon-Tae; Seo, Seong Jun; Kim, Seong‐Jin; Kim, Chang Deok

doi:10.1038/s41598-019-43209-3

Cited by 9 publications

(16 citation statements)

References 23 publications

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“…In other cell systems, TFG has been described as a negative regulator of the UPS, and its overexpression can lead to increased ER stress by interfering with ERAD [53]. Additionally, some non-immune secretory cells like insulin-producing β-cells [54] or sebocytes [55] also depend on TFG. While the functions of TFG may vary in different cell types and may depend on its abundance, all published data point to a function of TFG in homeostasis of the ER and the secretory pathway.…”

Section: Introductionmentioning

confidence: 99%

TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells

Steinmetz

Schlötzer‐Schrehardt²,

Hearne

et al. 2020

Autophagy

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Plasma cells depend on quality control of newly synthesized antibodies in the endoplasmic reticulum (ER) via macroautophagy/autophagy and proteasomal degradation. The cytosolic adaptor protein TFG (Trkfused gene) regulates ER-Golgi transport, the secretory pathway and proteasome activity in non-immune cells. We show here that TFG is upregulated during lipopolysaccharide-and CpG-induced differentiation of B1 and B2 B cells into plasmablasts, with the highest expression of TFG in mature plasma cells. CRISPR-CAS9-mediated gene disruption of tfg in the B lymphoma cell line CH12 revealed increased apoptosis, which was reverted by BCL2 but even more by ectopic TFG expression. Loss of TFG disrupted ER structure, leading to an expanded ER and increased expression of ER stress genes. When compared to wild-type CH12 cells, tfg KO CH12 cells were more sensitive toward ER stress induced by tunicamycin, monensin and proteasome inhibition or by expression of an ER-bound immunoglobulin (Ig) μ heavy (µH) chain. CH12 tfg KO B cells displayed more total LC3, lower LC3-II turnover and increased numbers and size of autophagosomes. Tandem-fluorescent-LC3 revealed less accumulation of GFP-LC3 in starved and chloroquine-treated CH12 tfg KO B cells. The GFP:RFP ratio of tandem-fluorescent-LC3 was higher in tunicamycin-treated CH12 tfg KO B cells, suggesting less autophagy flux during induced ER stress. Based on these data, we suggest that TFG controls autophagy flux in CH12 B cells and propose that TFG is a survival factor that alleviates ER stress through the support of autophagy flux in activated B cells and mature plasma cells.

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Section: Introductionmentioning

confidence: 99%

TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells

Steinmetz

Schlötzer‐Schrehardt²,

Hearne

et al. 2020

Autophagy

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“…Using an immortalized human sebocyte cell line that was established previously 7 , we first investigated the effect of azidothymidine on IGF-1-induced lipogenesis. The immortalized human sebocytes were treated with 10 or 25 µ M of azidothymidine.…”

Section: Resultsmentioning

confidence: 99%

“…Although IGF-1′s role in lipid production in sebocytes is well documented 7 14 , the role of IGF-1 in mitochondrial homeostasis in sebocytes has not been sufficiently investigated. In this study, we investigated the effect of IGF-1 on the mitochondria of sebocytes and found that IGF-1 increased the levels of PGC-1α and mtTFA in the immortalized human sebocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Immortalized human sebocytes were used for the experiment. The cell line was established as previously described 7 . The immortalized human sebocytes were cultured in Sebomed Medium (Biochrom, Berlin, Germany) supplemented with 10% fetal bovine serum (Gibco BRL, Rockville, MD, USA) and 5 ng/ml of recombinant human epidermal growth factor (Invitrogen, Grand Island, NY, USA).…”

Section: Methodsmentioning

confidence: 99%

“…For quantitative analysis of intracellular lipids, we performed thin-layer chromatography (TLC) as described previously 7 . In brief, immortalized human sebocytes were incubated with medium containing 2 µ Ci of 14 C-acetate and sodium salt (PerkinElmer, Boston, MA, USA) and incubated for 4 hours.…”

Section: Methodsmentioning

confidence: 99%

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Azidothymidine Downregulates Insulin-Like Growth Factor-1 Induced Lipogenesis by Suppressing Mitochondrial Biogenesis and Mitophagy in Immortalized Human Sebocytes

Yoo

Lee

et al. 2021

Ann Dermatol

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Background Increased sebum secretion is considered the main causative factor in the pathogenesis of acne. There is an unmet pharmacological need for a novel drug that can control sebum production with a favorable adverse effect profile. Objective To investigate the effect of azidothymidine on lipid synthesis in sebocytes and to identify the underlying mechanism of the inhibitory effect of azidothymidine on insulinlike growth factor (IGF)-1-induced lipid synthesis in sebocytes. Methods Immortalized human sebocytes were used for the analysis. Thin-layer chromatography (TLC) and Oil Red O staining were performed to evaluate lipid synthesis in the sebocytes. The differentiation, lipid synthesis, mitochondrial biogenesis, and mitophagy in sebocytes were investigated. Results TLC and Oil Red O staining revealed that azidothymidine reduced IGF-1 induced lipid synthesis in the immortalized human sebocytes. Azidothymidine also reduced IGF-1-induced expression of transcriptional factors and enzymes involved in sebocyte differentiation and lipid synthesis, respectively. Moreover, we found that IGF-1 upregulated the levels of peroxisome proliferator-activated receptorgamma coactivator-1α, LC-3B, p62, and Parkin, major regulators of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. In contrast, azidothymidine inhibited IGF-1 induced mitochondrial biogenesis and mitophagy in the sebocytes. Conclusion These results suggest that azidothymidine downregulates IGF-1-induced lipogenesis by dysregulating the quality of mitochondria through suppression of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. Our study provides early evidence that azidothymidine may be an effective candidate for a new pharmacological agent for controlling lipogenesis in sebocytes.

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Krüppel-like factor 4 (KLF4) facilitates lipid production in immortalized human sebocytes via regulating the expression of SREBP1

Zeng

Kim

et al. 2023

Biochemical and Biophysical Research Communications

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Tropomyosin-receptor kinase fused gene (TFG) regulates lipid production in human sebocytes

Cited by 9 publications

References 23 publications

TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells

TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells

Azidothymidine Downregulates Insulin-Like Growth Factor-1 Induced Lipogenesis by Suppressing Mitochondrial Biogenesis and Mitophagy in Immortalized Human Sebocytes

Krüppel-like factor 4 (KLF4) facilitates lipid production in immortalized human sebocytes via regulating the expression of SREBP1

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