Effect of GOLM1 gene knockout on renal fibrosis in mice with unilateral ureteral obstruction

doi:10.12307/2021.115

Abstract

Abstract:

BACKGROUND: Golgi membrane protein 1 (GOLM1) is widespread in human tissues, and its abnormal expression is closely related to cancer, viral infections and other diseases. Studies have shown that GOLM1 can regulate some fibrotic cytokines, but its role in renal fibrosis is unclear.

OBJECTIVE: To study the potential effects of GOLM1 on renal fibrosis in mice.
METHODS: Twelve 6-8-week-old GOLM1 knockout mice and 12 C57BL/6 wild type mice were selected and received an operation with left ureteral obstruction. The right kidney served as a control. The mice were sacrificed on the 4th day after the operation. The kidneys of the mice were divided into four groups: WT-C, WT-UUO, KO-C and KO-UUO. Hematoxylin-eosin staining and Masson staining were used to observe the renal tissue pathology and the degree of renal fibrosis. The mRNA expression of extracellular matrix components such as type I collagen α1 and fibronectin were detected by qRT-PCR. Flow cytometry was used to detect the proportion of macrophages. The expressions of inflammatory factors were detected by qRT-PCR. The study protocol was approved by the Experimental Animal Ethics Committee of Shanghai Jiaotong University.
RESULTS AND CONCLUSION: The kidneys of the WT-UUO and KO-UUO groups showed obvious kidney injury and renal interstitial fibrosis, and the expression of type I collagen α1 and fibronectin was remarkably increased. Compared with the WT-UUO group, the KO-UUO group had significantly severer renal damage, severer inflammatory cell infiltration and higher expression of extracellular matrix components (P < 0.05). There was no obvious renal injury, renal fibrosis, and extracellular matrix deposition in the kidneys of WT-C group and KO-C group. Compared with the WT-UUO group, the mRNA expression of interleukin-6, tumor necrosis factor α, interleukin 1β, C-C motif chemokine ligand 5 and monocyte chemotactic protein 1 increased significantly in the KO-UUO group (P < 0.05). Besides, the proportion of macrophage infiltration was also increased significantly in the KO-UUO group (P < 0.05). In the two control groups, there was less macrophage infiltration and low expression of inflammatory mediators in the renal tissue. To conclude, GOLM1 plays a protective role in the development of renal fibrosis. Its mechanism may be related to macrophage infiltration and the regulation of inflammatory mediators.

Key words: gene, knockout, protein, ureteral obstruction, renal fibrosis, extracellular matrix, inflammation, macrophages

CLC Number:

Qin Jianfang, Wang Huan, Wu Bingbing, Ma Xiaojing. Effect of GOLM1 gene knockout on renal fibrosis in mice with unilateral ureteral obstruction[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(26): 4162-4167.

Figures/Tables 5

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