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Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature

BACKGROUND: ACAN heterozygous mutations can cause short stature in patients with or without advanced bone age and have recently attracted researchers' attention. Growth hormone can be used to treat short stature induced by ACAN mutations; however, few studies have focused on the underlying mech...

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Autores principales: Wu, Huiping, Wang, Chaoban, Yu, Shiwen, Ye, Xiaojun, Jiang, Yalan, He, Pingping, Shan, Xiaoou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9937877/
https://www.ncbi.nlm.nih.gov/pubmed/36597844
http://dx.doi.org/10.1002/jcla.24830
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author Wu, Huiping
Wang, Chaoban
Yu, Shiwen
Ye, Xiaojun
Jiang, Yalan
He, Pingping
Shan, Xiaoou
author_facet Wu, Huiping
Wang, Chaoban
Yu, Shiwen
Ye, Xiaojun
Jiang, Yalan
He, Pingping
Shan, Xiaoou
author_sort Wu, Huiping
collection PubMed
description BACKGROUND: ACAN heterozygous mutations can cause short stature in patients with or without advanced bone age and have recently attracted researchers' attention. Growth hormone can be used to treat short stature induced by ACAN mutations; however, few studies have focused on the underlying mechanism of this treatment. METHODS: Four patients with new mutations were reported based on clinical data and genetic tests. We investigated the expression and Gene Ontology biological process enrichment of ACAN and GH pathways based on GTEx databases through bioinformatics analyses. The effect of ACAN on the growth hormone response evaluated in ATDC5 cells with a growth hormone stimulation test. RESULTS: Four mutations were reported in this study: c.619C > A, c.1967A > G, c.1888G > A, and c.1308_1309del. All patients' heights were under −2.5 SD, with one had advanced bone age, and two had GH deficiency. Two individuals received growth hormone therapy acquired variable levels of height SD score improvement. ACAN and the GH pathway were strongly associated; ACAN does not affect GHR but regulates the response to GH. Downregulating ACAN inhibited ATDC5 cell proliferation induced by GH. CONCLUSION: ACAN is associated with the GH pathway, revealing the potential mechanism underlying GH‐targeted treatment for ACAN mutation‐induced short stature. GH‐promoting therapies may increase patients' heights.
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spelling pubmed-99378772023-02-19 Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature Wu, Huiping Wang, Chaoban Yu, Shiwen Ye, Xiaojun Jiang, Yalan He, Pingping Shan, Xiaoou J Clin Lab Anal Research Articles BACKGROUND: ACAN heterozygous mutations can cause short stature in patients with or without advanced bone age and have recently attracted researchers' attention. Growth hormone can be used to treat short stature induced by ACAN mutations; however, few studies have focused on the underlying mechanism of this treatment. METHODS: Four patients with new mutations were reported based on clinical data and genetic tests. We investigated the expression and Gene Ontology biological process enrichment of ACAN and GH pathways based on GTEx databases through bioinformatics analyses. The effect of ACAN on the growth hormone response evaluated in ATDC5 cells with a growth hormone stimulation test. RESULTS: Four mutations were reported in this study: c.619C > A, c.1967A > G, c.1888G > A, and c.1308_1309del. All patients' heights were under −2.5 SD, with one had advanced bone age, and two had GH deficiency. Two individuals received growth hormone therapy acquired variable levels of height SD score improvement. ACAN and the GH pathway were strongly associated; ACAN does not affect GHR but regulates the response to GH. Downregulating ACAN inhibited ATDC5 cell proliferation induced by GH. CONCLUSION: ACAN is associated with the GH pathway, revealing the potential mechanism underlying GH‐targeted treatment for ACAN mutation‐induced short stature. GH‐promoting therapies may increase patients' heights. John Wiley and Sons Inc. 2023-01-04 /pmc/articles/PMC9937877/ /pubmed/36597844 http://dx.doi.org/10.1002/jcla.24830 Text en © 2023 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Articles
Wu, Huiping
Wang, Chaoban
Yu, Shiwen
Ye, Xiaojun
Jiang, Yalan
He, Pingping
Shan, Xiaoou
Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature
title Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature
title_full Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature
title_fullStr Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature
title_full_unstemmed Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature
title_short Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature
title_sort downregulation of acan is associated with the growth hormone pathway and induces short stature
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9937877/
https://www.ncbi.nlm.nih.gov/pubmed/36597844
http://dx.doi.org/10.1002/jcla.24830
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