TY - JOUR

T1 - Huntington’s disease alters the dermal fibroblasts secretome

AU - Хотин, М.

AU - Красковская , Н.

AU - Парфенова, Полина Сергеевна

AU - Юдинцева, Н.

AU - Колесниченко, Юлия Валерьевна

AU - Овчаренко, Елизавета Александровна

AU - Репкин, Егор Алексеевич

AU - Шабельников , С.

AU - Миттенберг , А.

AU - Михайлова, Наталья Аркадьевна

PY - 2023/12/28

Y1 - 2023/12/28

N2 - Abstract: Huntington’s disease is a hereditary incurable neurodegenerative disease caused by expansion of the polyglutamine tract in exon 1 of the huntingtin gene. Huntingtin is a large protein involved in many cellular processes, such as division, transport and secretion. Mutations in the protein lead to disruption of many cellular processes, including secretion, but differences in the composition of the secretome of cells in normal conditions and in Huntington’s disease remain poorly studied. Since huntingtin is expressed at high levels in peripheral tissues and in the skin, we have focused our attention on the study of secretome produced by dermal fibroblasts. In order to identify differences in secreted factors caused by the huntingtin mutation we used tandem time-of-flight mass spectrometry. Forty-two differential proteins were identified in the secretomes of dermal fibroblasts from healthy donor and patient with Huntington’s disease. We examine several proteins of interest including filamin A, periostin, ACTN4, BASP1, adrenomedullin, HSP70 and 14-3-3, whose expression is associated with processes such as cytoskeletal organization, cell adhesion, proliferation, cell migration, protein binding and regulation of cytoskeletal structure. HSP70 and 14-3-3 have neuroprotective properties, and interestingly, their expression was not detected in the secretome of cells with Huntington’s disease. Thus, it was shown that the set of proteins secreted into the extracellular space by dermal fibroblasts with the Huntington’s disease genotype differs from healthy cells, and the differences in cellular processes (proliferation, migration) observed in these cells in vitro are probably due to differences in the composition of the extracellular matrix which they synthesize.

AB - Abstract: Huntington’s disease is a hereditary incurable neurodegenerative disease caused by expansion of the polyglutamine tract in exon 1 of the huntingtin gene. Huntingtin is a large protein involved in many cellular processes, such as division, transport and secretion. Mutations in the protein lead to disruption of many cellular processes, including secretion, but differences in the composition of the secretome of cells in normal conditions and in Huntington’s disease remain poorly studied. Since huntingtin is expressed at high levels in peripheral tissues and in the skin, we have focused our attention on the study of secretome produced by dermal fibroblasts. In order to identify differences in secreted factors caused by the huntingtin mutation we used tandem time-of-flight mass spectrometry. Forty-two differential proteins were identified in the secretomes of dermal fibroblasts from healthy donor and patient with Huntington’s disease. We examine several proteins of interest including filamin A, periostin, ACTN4, BASP1, adrenomedullin, HSP70 and 14-3-3, whose expression is associated with processes such as cytoskeletal organization, cell adhesion, proliferation, cell migration, protein binding and regulation of cytoskeletal structure. HSP70 and 14-3-3 have neuroprotective properties, and interestingly, their expression was not detected in the secretome of cells with Huntington’s disease. Thus, it was shown that the set of proteins secreted into the extracellular space by dermal fibroblasts with the Huntington’s disease genotype differs from healthy cells, and the differences in cellular processes (proliferation, migration) observed in these cells in vitro are probably due to differences in the composition of the extracellular matrix which they synthesize.

KW - Huntington disease

KW - extracellular matrix

KW - neurodegeneration

KW - neuroprotective

KW - proliferation

KW - secretome

UR - https://www.mendeley.com/catalogue/4e6c4286-8f85-3c8d-ac98-a97f2285a51a/

U2 - 10.1134/s106816202310045x

DO - 10.1134/s106816202310045x

M3 - Article

VL - 49

SP - 241

EP - 250

JO - Russian Journal of Bioorganic Chemistry

JF - Russian Journal of Bioorganic Chemistry

SN - 1068-1620

IS - 1

ER -