Specific inhibitor of Smad3 (SIS3) alleviated submandibular gland fibrosis and dysfunction after dominant duct ligation in mice
Background/purpose: Chronic obstructive sialadenitis (COS) is a condition that severely reduced patients’ quality of life. This study aimed to analyze the effects of SIS3, a specific inhibitor of small mothers against decapentaplegic 3 (SMAD3), on the submandibular gland (SMG) dysfunction, fibrosis,...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Journal of Dental Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1991790223000417 |
| _version_ | 1797862210536472576 |
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| author | Honglin Li Guanru Wang Minqi Hu Runnan Dai Chunjie Li Yubin Cao |
| author_facet | Honglin Li Guanru Wang Minqi Hu Runnan Dai Chunjie Li Yubin Cao |
| author_sort | Honglin Li |
| collection | DOAJ |
| description | Background/purpose: Chronic obstructive sialadenitis (COS) is a condition that severely reduced patients’ quality of life. This study aimed to analyze the effects of SIS3, a specific inhibitor of small mothers against decapentaplegic 3 (SMAD3), on the submandibular gland (SMG) dysfunction, fibrosis, and inflammation. Materials and methods: The dominant duct in the SMG was ligated in mice, followed by intraperitoneal injection of SIS3 (2 mg/kg/day) or Dimethyl sulfoxide (DMSO) saline for 7 days. In the sham group, this duct was surgically identified but not ligated. Saliva flow, histological structure, fibrosis, Transforming growth factor-β1 (TGF-β)/SMAD3 signaling, and inflammatory cytokines, were analyzed. Results: SIS3 rescued ligation-induced SMG dysfunction and improved the saliva flow rate compared to DMSO. SIS3 alleviated acinar atrophy and ductal dilation and maintained the morphology of the basal membrane. SIS3 reduces interlobular and intralobular fibrosis and collagen deposition. We observed reduced SMAD3 phosphorylation and TGF-β expression. The SIS3 group showed downregulation of np_5318 and miR-21 and upregulation of miR-29 b compared to the DMSO group. Moreover, SIS3 controlled the inflammatory cytokine release, including interleukin-6 and interleukin-1β. Conclusion: SIS3 protected duct-ligated SMGs against fibrosis and dysfunction by inhibiting the TGF-β/SMAD3 signaling and inflammatory cytokine expression. SIS3 may serve as a promising treatment for chronic obstructive sialadenitis. |
| first_indexed | 2024-04-09T22:15:34Z |
| format | Article |
| id | doaj.art-d8e51dbbd5de42caa17ed2561c80d08c |
| institution | Directory Open Access Journal |
| issn | 1991-7902 |
| language | English |
| last_indexed | 2024-04-09T22:15:34Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Dental Sciences |
| spelling | doaj.art-d8e51dbbd5de42caa17ed2561c80d08c2023-03-23T04:35:25ZengElsevierJournal of Dental Sciences1991-79022023-04-01182865871Specific inhibitor of Smad3 (SIS3) alleviated submandibular gland fibrosis and dysfunction after dominant duct ligation in miceHonglin Li0Guanru Wang1Minqi Hu2Runnan Dai3Chunjie Li4Yubin Cao5State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Corresponding author. West China Hospital of Stomatology, Sichuan University, No.14, Section 3rd, Renmin Nan Road, Chengdu, 610041, China.State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Corresponding author. West China Hospital of Stomatology, Sichuan University, No.14, Section 3rd, Renmin Nan Road, Chengdu, 610041, China.Background/purpose: Chronic obstructive sialadenitis (COS) is a condition that severely reduced patients’ quality of life. This study aimed to analyze the effects of SIS3, a specific inhibitor of small mothers against decapentaplegic 3 (SMAD3), on the submandibular gland (SMG) dysfunction, fibrosis, and inflammation. Materials and methods: The dominant duct in the SMG was ligated in mice, followed by intraperitoneal injection of SIS3 (2 mg/kg/day) or Dimethyl sulfoxide (DMSO) saline for 7 days. In the sham group, this duct was surgically identified but not ligated. Saliva flow, histological structure, fibrosis, Transforming growth factor-β1 (TGF-β)/SMAD3 signaling, and inflammatory cytokines, were analyzed. Results: SIS3 rescued ligation-induced SMG dysfunction and improved the saliva flow rate compared to DMSO. SIS3 alleviated acinar atrophy and ductal dilation and maintained the morphology of the basal membrane. SIS3 reduces interlobular and intralobular fibrosis and collagen deposition. We observed reduced SMAD3 phosphorylation and TGF-β expression. The SIS3 group showed downregulation of np_5318 and miR-21 and upregulation of miR-29 b compared to the DMSO group. Moreover, SIS3 controlled the inflammatory cytokine release, including interleukin-6 and interleukin-1β. Conclusion: SIS3 protected duct-ligated SMGs against fibrosis and dysfunction by inhibiting the TGF-β/SMAD3 signaling and inflammatory cytokine expression. SIS3 may serve as a promising treatment for chronic obstructive sialadenitis.http://www.sciencedirect.com/science/article/pii/S1991790223000417SIS3Salivary glandsObstructive sialadenitisFibrosisTransforming growth factor betaSMAD3 |
| spellingShingle | Honglin Li Guanru Wang Minqi Hu Runnan Dai Chunjie Li Yubin Cao Specific inhibitor of Smad3 (SIS3) alleviated submandibular gland fibrosis and dysfunction after dominant duct ligation in mice Journal of Dental Sciences SIS3 Salivary glands Obstructive sialadenitis Fibrosis Transforming growth factor beta SMAD3 |
| title | Specific inhibitor of Smad3 (SIS3) alleviated submandibular gland fibrosis and dysfunction after dominant duct ligation in mice |
| title_full | Specific inhibitor of Smad3 (SIS3) alleviated submandibular gland fibrosis and dysfunction after dominant duct ligation in mice |
| title_fullStr | Specific inhibitor of Smad3 (SIS3) alleviated submandibular gland fibrosis and dysfunction after dominant duct ligation in mice |
| title_full_unstemmed | Specific inhibitor of Smad3 (SIS3) alleviated submandibular gland fibrosis and dysfunction after dominant duct ligation in mice |
| title_short | Specific inhibitor of Smad3 (SIS3) alleviated submandibular gland fibrosis and dysfunction after dominant duct ligation in mice |
| title_sort | specific inhibitor of smad3 sis3 alleviated submandibular gland fibrosis and dysfunction after dominant duct ligation in mice |
| topic | SIS3 Salivary glands Obstructive sialadenitis Fibrosis Transforming growth factor beta SMAD3 |
| url | http://www.sciencedirect.com/science/article/pii/S1991790223000417 |
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