An Update on Nontumorous Disorders of the Salivary Glands and Their Management for Internists

Daniels, Kelly; Schaitkin, Barry M.

doi:10.1016/j.mcna.2021.05.006

Cited by 1 publication

(1 citation statement)

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“…Both progressive interstitial fibrosis and parenchymal cell atrophy are salient indicators of pathological remodeling, leading to diminished glandular function. Contemporary clinical treatments for salivary gland diseases-encompassing endoscopy, Botox injections, and surgical interventions-have not yielded consistently promising outcomes [3]. As such, understanding the molecular mechanisms behind fibrosis progression and identifying effective pharmacological inhibitors remain paramount in salivary gland disease therapy.…”

Section: Introductionmentioning

confidence: 99%

Metformin Attenuates TGF-β1-Induced Fibrosis in Salivary Gland: A Preliminary Study

Wang,

Zhong,

Wang

et al. 2023

IJMS

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Fibrosis commonly arises from salivary gland injuries induced by factors such as inflammation, ductal obstruction, radiation, aging, and autoimmunity, leading to glandular atrophy and functional impairment. However, effective treatments for these injuries remain elusive. Transforming growth factor-beta 1 (TGF-β1) is fundamental in fibrosis, advancing fibroblast differentiation into myofibroblasts and enhancing the extracellular matrix in the salivary gland. The involvement of the SMAD pathway and reactive oxygen species (ROS) in this context has been postulated. Metformin, a type 2 diabetes mellitus (T2DM) medication, has been noted for its potent anti-fibrotic effects. Through human samples, primary salivary gland fibroblasts, and a rat model, this study explored metformin’s anti-fibrotic properties. Elevated levels of TGF-β1 (p < 0.01) and alpha-smooth muscle actin (α-SMA) (p < 0.01) were observed in human sialadenitis samples. The analysis showed that metformin attenuates TGF-β1-induced fibrosis by inhibiting SMAD phosphorylation (p < 0.01) through adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)-independent pathways and activating the AMPK pathway, consequently suppressing NADPH oxidase 4 (NOX4) (p < 0.01), a main ROS producer. Moreover, in rats, metformin not only reduced glandular fibrosis post-ductal ligation but also protected acinar cells from ligation-induced injuries, thereby normalizing the levels of aquaporin 5 (AQP5) (p < 0.05). Overall, this study underscores the potential of metformin as a promising therapeutic option for salivary gland fibrosis.

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Section: Introductionmentioning

confidence: 99%