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.

Bardet-Biedl综合征（BBS）是一种以纤毛病为主的遗传性疾病，累及多效性多系统表型，包括脂肪、神经、视网膜、肾脏等。因此，其特点是肥胖、认知障碍以及视网膜、肾脏和皮肤异常。包括我们在内的初步研究表明，BBS基因在脂肪细胞和 β 细胞的早期发育阶段发挥作用。然而，这种在其他 BBS 相关组织中的作用尚不清楚。

我们研究了参与不同 BBS 细胞类型增殖和早期分化的BBS基因。

在七个体外和转基因细胞模型中研究了BBS基因在细胞增殖中的参与；角质形成细胞 ( hHaCaT ) 和 Ras 转染的角质形成细胞 ( Ras-hHaCaT )、神经元细胞系 ( hSH-SY5Y和rPC-12 )、沉默的BBS4神经细胞系 (s iBbs4 hSH-SY5Y和siBbs4 rPC-12 )、脂肪细胞 ( m3T3L1 ) ，以及使用分子和生物化学方法从BBS4患者获得的离体转化 B 细胞。

RashHaCaT细胞的增殖速度加快，同时BBS1、2和4的转录水平显着降低。使用化学（CDK4 抑制剂）和血清剥夺方法将BBS1、2 和 4转录物与hHaCaT细胞周期停滞（G1 期）相关联。脂肪细胞 ( m3T3-L1 ) Bbs1、2和4转录物水平对应于细胞周期阶段（CDK4 抑制剂和血清剥夺）。SiBBS4 hSH-SY5Y细胞表现出早期细胞增殖和分化（伤口愈合测定）率。SiBbs4 rPC-12模型表现出与 Nestin 表达水平相对应的显着增殖和分化率。BBS4患者转化的 B 细胞表现出加速的增殖率（LPS 诱导方法）。

总之，BBS4基因在各种BBS相关组织的细胞增殖中发挥着显着的、相似的和全局的作用。这些结果凸显了BBS基因在细胞周期中的普遍作用，并进一步加深了对BBS发育机制的认识。