PMID- 30278995 OWN - NLM STAT- MEDLINE DCOM- 20190208 LR - 20211204 IS - 1618-0372 (Electronic) IS - 0065-1281 (Linking) VI - 120 IP - 8 DP - 2018 Nov TI - Differential expression of mTOR signaling pathway proteins in lichen planopilaris and frontal fibrosing alopecia. PG - 837-845 LID - S0065-1281(18)30175-2 [pii] LID - 10.1016/j.acthis.2018.09.007 [doi] AB - Dysregulation of the mammalian target of rapamycin (mTOR) signaling pathway has a variety of effects on the immune system and stem cell proliferation. Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are inflammatory scalp conditions resulting in permanent alopecia, which are thought to be related to stem cell damage. Here we investigate the expression of mTOR signaling pathway proteins in human hair follicles of LPP and FFA patients. The expression of mTOR pathway proteins in biopsy specimens from lesional and non-lesional scalp areas of eight LPP and five FFA patients were compared to control scalp biopsies from patients undergoing surgical excisions of sebaceous cysts. We performed immunohistochemical evaluation using a panel of antibodies including mTOR, phospho-mTOR (Ser2448), phospho-p70S6K (Thr389), phospho-4EBP1 (Thr37146), and phospho-tuberin (T1462), as well as Western blot analysis for phospho-p70S6K (Thr389) expression. All evaluated mTOR pathway proteins were similarly expressed in the control and patient non-lesional scalps. While mTOR expression did not show significant alterations between the groups, p-mTOR, p-p70S6K, p-4EBP1, and p-tuberin expressions decreased in the interfollicular epidermis in the lesional scalps of patients. p-p70S6K and p-4EBP1 expression decreased in the outer root sheath (ORS) and inner root sheath (IRS) of the bulge of hair follicles in the lesional scalps of patients. p-mTOR and p-p70S6K expression increased in the lower follicle ORS and bulb of the hair follicles, and p-4EBP1 expression decreased in the bulb of the hair follicles in the lesional scalps of patients. Phospho-tuberin expression increased in the IRS of the bulge and lower follicle ORS of the hair follicles in the lesional scalps of patients, whereas its expression decreased in the bulb. Our results indicate that the mTOR signaling pathway proteins are localized throughout normal hair follicles and that expression of mTOR signaling pathway proteins is altered in the hair follicles of LPP and FFA patients. Further research is required to understand the mechanism by which mTOR operates in the pathogenesis of these diseases. CI - Copyright (c) 2018 Elsevier GmbH. All rights reserved. FAU - Dicle, Ozlem AU - Dicle O AD - Akdeniz University School of Medicine, Department of Dermatology and Venereology, Antalya, Turkey. Electronic address: odicle@akdeniz.edu.tr. FAU - Celik-Ozenci, Ciler AU - Celik-Ozenci C AD - Akdeniz University School of Medicine, Department of Histology and Embryology, Antalya, Turkey. FAU - Sahin, Pinar AU - Sahin P AD - Akdeniz University School of Medicine, Department of Histology and Embryology, Antalya, Turkey. FAU - Pfannes, Eva Katharina Barbosa AU - Pfannes EKB AD - Charite-Universitatsmedizin, Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science, Berlin, Germany. FAU - Vogt, Annika AU - Vogt A AD - Charite-Universitatsmedizin, Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science, Berlin, Germany. FAU - Altinok, Berna Nazlim AU - Altinok BN AD - Akdeniz University School of Medicine, Department of Dermatology and Venereology, Antalya, Turkey. FAU - Blume-Peytavi, Ulrike AU - Blume-Peytavi U AD - Charite-Universitatsmedizin, Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science, Berlin, Germany. LA - eng PT - Journal Article DEP - 20180929 PL - Germany TA - Acta Histochem JT - Acta histochemica JID - 0370320 RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - Lichen planus follicularis SB - IM MH - *Alopecia/metabolism/pathology MH - Blotting, Western MH - Female MH - Hair Follicle/pathology MH - Humans MH - Immunohistochemistry MH - *Lichen Planus/metabolism MH - Reference Standards MH - Signal Transduction MH - TOR Serine-Threonine Kinases/*metabolism OTO - NOTNLM OT - Frontal fibrosing alopecia OT - Hair follicle OT - Lichen planopilaris OT - Primary cicatricial alopecia OT - mTOR signaling pathway EDAT- 2018/10/04 06:00 MHDA- 2019/02/09 06:00 CRDT- 2018/10/04 06:00 PHST- 2018/05/22 00:00 [received] PHST- 2018/09/20 00:00 [revised] PHST- 2018/09/20 00:00 [accepted] PHST- 2018/10/04 06:00 [pubmed] PHST- 2019/02/09 06:00 [medline] PHST- 2018/10/04 06:00 [entrez] AID - S0065-1281(18)30175-2 [pii] AID - 10.1016/j.acthis.2018.09.007 [doi] PST - ppublish SO - Acta Histochem. 2018 Nov;120(8):837-845. doi: 10.1016/j.acthis.2018.09.007. Epub 2018 Sep 29.