Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu 610041, China.
Exp Biol Med (Maywood). 2021 Jun;246(11):1269-1273. doi: 10.1177/1535370221993430. Epub 2021 Feb 27.
Submandibular glands have essential functions in taste, mastication, swallowing, and digestion. Submandibular gland hypofunction is prevalent in the elderly, impairing the patients' quality of life. Current clinical treatment strategies have not decelerated or reversed the pathological process of submandibular gland hypofunction. Therefore, novel restoration strategies should be explored. However, studies on the mechanism of aging-related submandibular gland hypofunction remain very limited. The role of the TGF-β/Smad pathway in fibrosis has been studied in other organs. Therefore, this study aimed to elucidate the role of TGF-β/Smad signaling in the aging-related submandibular gland hypofunction. The results showed that Smad7 knockout in mice decreased the salivary flow rate. H&E, Masson trichrome, and immunohistochemistry staining of MCP-1 and α-SMA showed that Smad7 knockout in mice resulted in lymphocytic infiltration, acinar cell atrophy, and interstitial fibrosis. The Western blotting of collagen I and III also confirmed extensive fibrosis. We then found that Smad7 depletion resulted in the TGF-β-mediated fibrosis via mir-21, mir-29, and np_5318, and NFκB-driven inflammation activation. This study confirmed the inhibitory role of Smad7 in the aging-related submandibular gland hypofunction. Therefore, it provided a promising treatment target for aging-related dysfunction and sialadenitis of submandibular gland.
下颌下腺在味觉、咀嚼、吞咽和消化中具有重要功能。下颌下腺功能减退在老年人中很常见，会降低患者的生活质量。目前的临床治疗策略并没有延缓或逆转下颌下腺功能减退的病理过程。因此，应该探索新的修复策略。然而，关于与年龄相关的下颌下腺功能减退的机制研究仍然非常有限。TGF-β/Smad 途径在其他器官的纤维化中作用已经得到了研究。因此，本研究旨在阐明 TGF-β/Smad 信号通路在与年龄相关的下颌下腺功能减退中的作用。结果表明，在小鼠中敲除 Smad7 会降低唾液流量。H&E、Masson 三色和 MCP-1 和 α-SMA 的免疫组化染色显示，Smad7 敲除的小鼠会导致淋巴细胞浸润、腺泡细胞萎缩和间质纤维化。胶原 I 和 III 的 Western blot 也证实了广泛的纤维化。然后我们发现，Smad7 耗竭通过 mir-21、mir-29 和 np_5318 以及 NFκB 驱动的炎症激活导致 TGF-β 介导的纤维化。本研究证实了 Smad7 在与年龄相关的下颌下腺功能减退中的抑制作用。因此，它为与年龄相关的功能障碍和下颌下腺唾液腺炎提供了有前途的治疗靶点。
