Adipose-derived stem cells postpone the progression of Sjögren's syndrome by upregulating the Hippo signaling pathway

Zizhan Li; Xinli Fan; Xiuying Xu; Qin Zhou; Guimiao Xing; Gangli Liu

doi:10.3892/etm.2022.11524

Adipose-derived stem cells postpone the progression of Sjögren's syndrome by upregulating the Hippo signaling pathway

Exp Ther Med. 2022 Jul 22;24(3):587. doi: 10.3892/etm.2022.11524. eCollection 2022 Sep.

Authors

Zizhan Li¹, Xinli Fan¹, Xiuying Xu², Qin Zhou³, Guimiao Xing⁴, Gangli Liu¹

Affiliations

¹ Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.
² Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.
³ Department of VIP Venter, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.
⁴ Department of Oral Pathology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.

Abstract

The aim of the present study was to explore the effect and mechanism of action of adipose-derived stem cells (ADSCs) on Sjögren syndrome (SS) to develop novel and more effective methods for SS treatment. ADSCs, dexamethasone or normal saline was injected into the submandibular gland (SMG) of three 12-week-old non-obese diabetic (NOD) mice. The degree of lymphocyte infiltration was considered as a criterion for judging disease progression, hematoxylin and eosin staining was performed to observe the pathological state, and the expression levels of TAZ, E-cadherin and α-catenin were assessed by western blotting. ADSC transplantation triggered an inhibitory effect on the progression of SS, which was slightly stronger compared with that of dexamethasone treatment. This was found to be related to the Hippo signaling pathway. In addition, TAZ protein expression levels decreased gradually with the progression of the disease; immunofluorescence staining showed that the expression of E-cadherin and TAZ followed similar trends. Notably, the expression of TAZ, p-TAZ, E-cadherin and α-catenin in NOD mice were lower compared with that in Control mice. Similarly, the ratio of p-TAZ/TAZ also decreased, which means that the activation level of Hippo signal pathway decreased. The results suggest that ADSCs may exert a therapeutic effect against SS and may postpone its progression by upregulating the Hippo signaling pathway.

Keywords: Hippo signaling pathway; Sjögren's syndrome; adipose-derived stem cell.

Grants and funding

Funding: The present study was supported by The National Natural Science Foundation of China (grant no. 81402298), The Young Scholars Program of the Shandong University and the opening project of The Collaborative Innovation Center for Classic and Famous Prescriptions of Traditional Chinese Medicine in Shandong Province entitled ‘Functional mechanism of Chaihu Guizhi Ganjiang Decoction in the treatment of Sjögren's syndrome’ (grant no. 2019KFY10). The present study was also supported by the project ‘Research on the functional mechanism of stem cell exosomes in the treatment of Sjögren's syndrome’ of Shandong Jiekai Biotechnology Co., Ltd.