KIAA0753 promotes glucose and energy metabolism in osteoblasts inhibited by diabetes

Mengxue LI; Jichun WANG; Letai LI; Changdong WANG

doi:10.16016/j.2097-0927.202403024

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KIAA0753 promotes glucose and energy metabolism in osteoblasts inhibited by diabetes

Basic Medicine | 更新时间：2026-01-09

- KIAA0753 promotes glucose and energy metabolism in osteoblasts inhibited by diabetes
- Journal of Army Medical University Vol. 46, Issue 20, Pages: 2291-2300(2024)
- 作者机构：
  
  1.400016 重庆，重庆医科大学基础医学院分子医学与肿瘤研究中心
  2.400016 重庆，重庆医科大学生物化学与分子生物学教研室
- 作者简介：
- 基金信息：
  
  the "Chunhui Plan" Collaborative Research Project of Ministry of Education in 2022(2022-2);the General Program of Chongqing Science and Technology Commission(CSTB2022NSCQ-MSX0945);the College Student Innovation Project of Chongqing in 2023(202337)
- DOI：10.16016/j.2097-0927.202403024
  CLC： R343.23;R730.23;R737.25
- Received：07 March 2024，
  
  Revised：2024-06-10，
  
  Published：30 October 2024
- 稿件说明：
移动端阅览
Mengxue LI, Jichun WANG, Letai LI, et al. KIAA0753 promotes glucose and energy metabolism in osteoblasts inhibited by diabetes[J]. Journal of Army Medical University, 2024, 46(20): 2291-2300.
DOI：

Mengxue LI, Jichun WANG, Letai LI, et al. KIAA0753 promotes glucose and energy metabolism in osteoblasts inhibited by diabetes[J]. Journal of Army Medical University, 2024, 46(20): 2291-2300. DOI： 10.16016/j.2097-0927.202403024.

摘要

目的

探讨KIAA0753对成骨细胞MC3T3-E1糖代谢及能量代谢的影响。

方法

由基因表达综合数据库(Gene Expression Omnibus，GEO)获取Joubert综合征患者基因表达数据集GSE182286并对其进行分析。构建KIAA0753过表达载体，实验分为对照组、高糖组和高糖+过表达KIAA0753组，采用Western blot检测在高糖条件下KIAA0753对MC3T3-E1细胞糖代谢相关蛋白糖原合酶1(glycogen synthase 1

GYS1)、糖原磷酸化酶L(glycogen phosphorylase L

PYGL)、葡萄糖转运蛋白4(glucose transporter type 4

GluT4)、磷酸果糖激酶(phosphofructokinase muscle

PFKM)、丙酮酸脱氢酶磷酸酶1(pyruvate dehydrogenase phosphatase 1

PDP1)、乙酰辅酶A羧化酶α(acetyl-CoA carboxylase α

ACACA)，以及线粒体相关蛋白过氧化物酶体增殖激活受体γ(peroxisome proliferator-activated receptor-γ coactivator-1α

PGC-1α)、核呼吸因子1(nuclear respiratory factor 1

NRF1)、线粒体转录因子A(mitochondrial transcription factor A

TFAM)的影响；通过检测细胞培养基中葡萄糖含量、细胞内的糖原含量和乳酸含量评估KIAA0753对糖代谢中间产物的影响；采用细胞免疫荧光和ATP含量检测KIAA0753对线粒体活性及功能的影响；采用EdU染色检测KIAA0753对成骨细胞MC3T3-E1增殖的影响。

结果

KIAA0753在Joubert综合症患者和高糖条件下表达下调(

＜0.05)。高糖抑制蛋白GYS1、ACACA、PFKM、GluT4、PGC-1α、TFAM和NRF1的表达，促进蛋白PDP1和PYGL的表达，减少糖原生成和细胞外葡萄糖的消耗，促进乳酸生成，而过表达KIAA0753后减缓了高糖的作用，促进蛋白GYS1、ACACA、PFKM、GluT4、PGC-1α、TFAM和NRF1的表达，抑制蛋白PDP1和PYGL的表达，增加糖原生成和细胞外葡萄糖的消耗，抑制乳酸生成(

＜0.05)。与高糖组相比，过表达KIAA0753在高糖条件下显著提升MC3T3-E1细胞线粒体的活性和膜电位，促进ATP的合成(

＜0.05)，促进MC3T3-E1细胞的增殖(

＜0.05)。

结论

KIAA0753能够促进成骨细胞的糖代谢并提升线粒体活性和功能，从而为机体提供更多能量。

Abstract

Objective

To explore the effect of KIAA0753 on glucose and energy metabolism in mouse embryonic osteoblast precursor cell line MC3T3-E1.

Methods

The GSE182286 datasets of patients with Joubert syndrome acquired from the Gene Expression Comprehensive database were analyzed for the levels of gene expression. After the cells with KIAA0753 overexpression were constructed and the experiment were divided into the control group

the high glucose group and the high glucose+overexpression KIAA0753 group

Western blotting was used to determine the effect of KIAA0753 on MC3T3-E1 cells under high glucose condition by detecting the expression of the glucose metabolism-related proteins

such as glycogen synthase 1 (GYS1)

glycogen phosphorylase L (PYGL)

glucose transporter type 4(GluT4)

phosphofructokinase muscle (PFKM)

pyruvate dehydrogenase phosphatase 1 (PDP1)

and acetyl-CoA carboxylase α (ACACA)

as well as the mitochondria function-associated proteins

including peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)

nuclear respiratory factor 1 (NRF1)

and mitochondrial transcription factor A (TFAM). The effect of KIAA0753 on the intermediates of glucose metabolism was analyzed by determining the contents of glycogen

glucose and lactic acid in the cell culture medium. Cellular immunofluorescence assay and adenosine triphosphate (ATP) assay were employed to measure the mitochondrial activity and function impacted by KIAA0753 in the cells under high glucose condition. The effect of KIAA0753 on the proliferation of MC3T3-E1 cells under high glucose was detected by EdU staining.

Results

The expression of KIAA0753 protein was downregulated in patients with Joubert syndrome and in MC3T3-E1 cells under high glucose conditions (

0.05). High glucose

resulted in inhibited protein expression of GYS1

ACACA

PFKM

GluT4

PGC-1α

TFAM and NRF1

enhanced protein levels of PDP1 and PYGL

reduced glycogen generation and consumption of extracellular glucose

and promoted production of lactic acid (

0.05). While

overexpression of KIAA0753 could attenuate the effect of high glucose

that is

up-regulating the protein expression levels of GYS1

ACACA

PFKM

GluT4

PGC-1α

TFAM and NRF1

suppressing those of PDP1 and PYGL

enhancing glycogen generation and consumption of extracellular glucose

and inhibiting production of lactic acid (

0.05). What's more

the overexpression also could elevate the activity and membrane potential of mitochondria

and promote the ATP synthesis (

0.05) and cell proliferation (

0.05) in MC3T3-E1 cells under high glucose.

Conclusion

KIAA0753 can promote glucose metabolism and improve mitochondrial activity and function in osteoblasts

consequently providing more energy to the body.

关键词

Keywords

references

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