Involvement of TGF-β and Autophagy Pathways in Pathogenesis of Diabetes: A Comprehensive Review on Biological and Pharmacological Insights

Abstract

Despite recent advancements in clinical drugs, diabetes treatment still needs further progress. As such, ongoing research has attempted to determine the precise molecular mechanisms of the disorder. Specifically, evidence supports that several signaling pathways play pivotal roles in the development of diabetes. However, the exact molecular mechanisms of diabetes still need to be explored. This study examines exciting new hallmarks for the strict involvement of autophagy and TGF-b signaling pathways in the pathogenesis of diabetes and the design of novel therapeutic strategies. Dysregulated autophagy in pancreatic b cells due to hyperglycemia, oxidative stress, and inflammation is associated with diabetes and accompanied by dysregulated autophagy in insulin target tissues and the progression of diabetic complications. Consequently, several therapeutic agents such as adiponectin, ezetimibe, GABA tea, geniposide, liraglutide, guava extract, and vitamin D were shown to inhibit diabetes and its complications through modulation of the autophagy pathway. Another pathway, TGF-b signaling pathway, appears to play a part in the progression of diabetes, insulin resistance, and autoimmunity in both type 1 and 2 diabetes and complications in diabetes. Subsequently, drugs that target TGF-b signaling, especially naturally derived ones such as resveratrol, puerarin, curcumin, hesperidin, and silymarin, as well as Propolis, Lycopus lucidus, and Momordica charantia extracts, may become promising alternatives to current drugs in diabetes treatment. This review provides keen insights into novel therapeutic strategies for the medical care of diabetes.

Relationship between Axial Length and Levels of TGF-β in the Aqueous Humor and Plasma of Myopic Patients

“…The patients with age-related cataract who underwent phacoemulsification were mostly of older age. They possibly have a higher prevalence of metabolic diseases (such as diabetes [ 43 ] and liver diseases [ 44 ]). Moreover, Zhu et al [ 45 ] found that in cataract patients, the concentration of TGF- β 2 decreased while nuclear color darkens.…”

Transforming Growth Factor-Beta (TGF-β) Signaling in Cancer-A Betrayal Within

“…TAK1 activates IKK, which in turn phosphorylate IκBα, leading to proteasomal degradation of IKBα and the release of NF-kB p65-p50 heterodimer resulting in NF-κB activation. ( Hydarpoor et al, 2020 ). Studies have demonstrated that TGF-TAK1 also induces NF-kB activation in murine B cells, hepatocytes and head and neck squamous cell carcinoma (HNSCC) cells ( Loren et al, 2021 ).…”

Bone marrow mesenchymal stem cells facilitate diabetic wound healing through the restoration of epidermal cell autophagy via the HIF-1α/TGF-β1/SMAD pathway

“…Instead, we found that CM from hypoxic BMSCs increased SMAD2 phosphorylation levels and SMAD4 localization in the nuclei of epidermal cells, suggesting SMAD pathway activation in epidermal cells. In TGF-β1/SMAD signaling, the binding of TGF-β1 to its receptor complex activates SMAD2/ SMAD3 through direct phosphorylation and further forms a trimer with SMAD4 that subsequently translocates into the nucleus to facilitate gene transcription [44]. Regarding the essential role of the TGF-β1/SMAD signaling pathway in the modulation of cellular behavior, we hypothesized that SMADs are the pivotal downstream mediators of epidermal cell autophagy activation in response to hypoxic BMSC-derived CM.…”