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Title: | Toll-like receptors 2 and 4 stress signaling and sodium-glucose cotransporter-2 in kidney disease |
Authors: | Gaikwad, Anil Bhanudas |
Keywords: | Pharmacy Kidney disease HMGB1 Sodium glucose co-transporter-2 inhibitors (SGLT2is) |
Issue Date: | Dec-2022 |
Publisher: | Springer |
Abstract: | Kidney disease is the 6th fastest-growing cause of death and a serious global health concern that urges effective therapeutic options. The inflammatory response is an initial reaction from immune and parenchymal cells in kidney diseases. Toll-like receptors (TLR) 2 and 4 are highly expressed by various kidney cells and respond to ‘signaling danger’ proteins, such as high mobility group box binding protein 1 (HMGB1) and prompt the progression of kidney disease by releasing inflammatory mediators. Burgeoning reports suggest that both SGLT2 and ER stress elevates TLR2/4 signaling via different axis. Moreover, SGLT2 signaling aggravates inflammation under the disease condition by promoting the NLR family pyrin domain-containing three inflammasomes and ER stress. Intriguingly, TLR2/4 downstream adaptors activate ER stress regulators. The above-discussed interactions imply that TLR2/4 does more than immune response during kidney disease. Here, we discuss in detail evidence of the roles and regulation of TLR2/4 in the context of a relationship between ER stress and SGLT2. Also, we highlighted different preclinical studies of SGLT2 inhibitors against TLR2/4 signaling in various kidney diseases. Moreover, we discuss the observational and interventional evidence about the relation between TLR2/4, ER stress, and SGLT2, which may represent the TLR2/4 as a potential therapeutic target for kidney disease. |
URI: | https://link.springer.com/article/10.1007/s11010-022-04652-5 http://dspace.bits-pilani.ac.in:8080/xmlui/handle/123456789/13509 |
Appears in Collections: | Department of Pharmacy |
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