{"title":"BBS 基因参与 BBS 相关组织的加速增殖和早期分化","authors":"Avital Horwitz , Noa Levi-Carmel , Olga Shnaider , Ruth Birk","doi":"10.1016/j.diff.2024.100745","DOIUrl":null,"url":null,"abstract":"<div><p>Bardet-Biedl syndrome (BBS) is an inherited disorder primarily ciliopathy with pleiotropic multi-systemic phenotypic involvement, including adipose, nerve, retinal, kidney, Etc. Consequently, it is characterized by obesity, cognitive impairment and retinal, kidney and cutaneous abnormalities. Initial studies, including ours have shown that <em>BBS</em> genes play a role in the early developmental stages of adipocytes and β-cells. However, this role in other BBS-related tissues is unknown.</p><p>We investigated <em>BBS</em> genes involvement in the proliferation and early differentiation of different BBS cell types.</p><p>The involvement of <em>BBS</em><span> genes in cellular proliferation were studied in seven </span><em>in-vitro</em><span><span> and transgenic cell models; </span>keratinocytes (</span><em>hHaCaT</em>) and Ras-transfected keratinocytes (<em>Ras-hHaCaT</em>), neuronal cell lines (<em>hSH-SY5Y</em> and <em>rPC-12</em>), silenced <span><em>BBS4</em></span> neural cell lines (s<em>iBbs4 hSH-SY5Y</em> and <em>siBbs4 rPC-12</em>), adipocytes (<em>m3T3L1</em>), and <em>ex-vivo</em> transformed B-cells obtain from <em>BBS4</em> patients, using molecular and biochemical methodologies.</p><p><em>RashHaCaT</em> cells showed an accelerated proliferation rate in parallel to significant reduction in the transcript levels of <span><em>BBS1</em><em>, 2</em></span>, and <em>4</em>. <em>BBS1, 2, and 4</em> transcripts linked with <em>hHaCaT</em><span> cell cycle arrest (G1 phase) using both chemical (CDK4 inhibitor) and serum deprivation methodologies. Adipocyte (</span><em>m3T3-L1</em>) <em>Bbs1, 2</em> and <em>4</em><span> transcript levels corresponded to the cell cycle phase (CDK4 inhibitor and serum deprivation). </span><em>SiBBS4 hSH-SY5Y</em> cells exhibited early cell proliferation and differentiation (wound healing assay) rates. <em>SiBbs4 rPC-12</em> models exhibited significant proliferation and differentiation rate corresponding to Nestin expression levels. <em>BBS4</em> patients-transformed B-cells exhibited an accelerated proliferation rate (LPS-induced methodology).</p><p>In conclusions, the <em>BBS4</em> gene plays a significant, similar and global role in the cellular proliferation of various BBS related tissues. These results highlight the universal role of the BBS gene in the cell cycle, and further deepen the knowledge of the mechanisms underlying the development of BBS.</p></div>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"BBS genes are involved in accelerated proliferation and early differentiation of BBS-related tissues\",\"authors\":\"Avital Horwitz , Noa Levi-Carmel , Olga Shnaider , Ruth Birk\",\"doi\":\"10.1016/j.diff.2024.100745\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Bardet-Biedl syndrome (BBS) is an inherited disorder primarily ciliopathy with pleiotropic multi-systemic phenotypic involvement, including adipose, nerve, retinal, kidney, Etc. Consequently, it is characterized by obesity, cognitive impairment and retinal, kidney and cutaneous abnormalities. Initial studies, including ours have shown that <em>BBS</em> genes play a role in the early developmental stages of adipocytes and β-cells. However, this role in other BBS-related tissues is unknown.</p><p>We investigated <em>BBS</em> genes involvement in the proliferation and early differentiation of different BBS cell types.</p><p>The involvement of <em>BBS</em><span> genes in cellular proliferation were studied in seven </span><em>in-vitro</em><span><span> and transgenic cell models; </span>keratinocytes (</span><em>hHaCaT</em>) and Ras-transfected keratinocytes (<em>Ras-hHaCaT</em>), neuronal cell lines (<em>hSH-SY5Y</em> and <em>rPC-12</em>), silenced <span><em>BBS4</em></span> neural cell lines (s<em>iBbs4 hSH-SY5Y</em> and <em>siBbs4 rPC-12</em>), adipocytes (<em>m3T3L1</em>), and <em>ex-vivo</em> transformed B-cells obtain from <em>BBS4</em> patients, using molecular and biochemical methodologies.</p><p><em>RashHaCaT</em> cells showed an accelerated proliferation rate in parallel to significant reduction in the transcript levels of <span><em>BBS1</em><em>, 2</em></span>, and <em>4</em>. <em>BBS1, 2, and 4</em> transcripts linked with <em>hHaCaT</em><span> cell cycle arrest (G1 phase) using both chemical (CDK4 inhibitor) and serum deprivation methodologies. Adipocyte (</span><em>m3T3-L1</em>) <em>Bbs1, 2</em> and <em>4</em><span> transcript levels corresponded to the cell cycle phase (CDK4 inhibitor and serum deprivation). </span><em>SiBBS4 hSH-SY5Y</em> cells exhibited early cell proliferation and differentiation (wound healing assay) rates. <em>SiBbs4 rPC-12</em> models exhibited significant proliferation and differentiation rate corresponding to Nestin expression levels. <em>BBS4</em> patients-transformed B-cells exhibited an accelerated proliferation rate (LPS-induced methodology).</p><p>In conclusions, the <em>BBS4</em> gene plays a significant, similar and global role in the cellular proliferation of various BBS related tissues. These results highlight the universal role of the BBS gene in the cell cycle, and further deepen the knowledge of the mechanisms underlying the development of BBS.</p></div>\",\"PeriodicalId\":2,\"journal\":{\"name\":\"ACS Applied Bio Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Bio Materials\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S030146812400001X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S030146812400001X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
BBS genes are involved in accelerated proliferation and early differentiation of BBS-related tissues
Bardet-Biedl syndrome (BBS) is an inherited disorder primarily ciliopathy with pleiotropic multi-systemic phenotypic involvement, including adipose, nerve, retinal, kidney, Etc. Consequently, it is characterized by obesity, cognitive impairment and retinal, kidney and cutaneous abnormalities. Initial studies, including ours have shown that BBS genes play a role in the early developmental stages of adipocytes and β-cells. However, this role in other BBS-related tissues is unknown.
We investigated BBS genes involvement in the proliferation and early differentiation of different BBS cell types.
The involvement of BBS genes in cellular proliferation were studied in seven in-vitro and transgenic cell models; keratinocytes (hHaCaT) and Ras-transfected keratinocytes (Ras-hHaCaT), neuronal cell lines (hSH-SY5Y and rPC-12), silenced BBS4 neural cell lines (siBbs4 hSH-SY5Y and siBbs4 rPC-12), adipocytes (m3T3L1), and ex-vivo transformed B-cells obtain from BBS4 patients, using molecular and biochemical methodologies.
RashHaCaT cells showed an accelerated proliferation rate in parallel to significant reduction in the transcript levels of BBS1, 2, and 4. BBS1, 2, and 4 transcripts linked with hHaCaT cell cycle arrest (G1 phase) using both chemical (CDK4 inhibitor) and serum deprivation methodologies. Adipocyte (m3T3-L1) Bbs1, 2 and 4 transcript levels corresponded to the cell cycle phase (CDK4 inhibitor and serum deprivation). SiBBS4 hSH-SY5Y cells exhibited early cell proliferation and differentiation (wound healing assay) rates. SiBbs4 rPC-12 models exhibited significant proliferation and differentiation rate corresponding to Nestin expression levels. BBS4 patients-transformed B-cells exhibited an accelerated proliferation rate (LPS-induced methodology).
In conclusions, the BBS4 gene plays a significant, similar and global role in the cellular proliferation of various BBS related tissues. These results highlight the universal role of the BBS gene in the cell cycle, and further deepen the knowledge of the mechanisms underlying the development of BBS.
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