Publications by authors named "Sandeep M Subrahmanian"
Sterile inflammation resulting in an altered immune response is a key determinant of renal injury in diabetic nephropathy (DN). In this investigation, we evaluated the hypothesis that hyperglycemic conditions augment the pro-inflammatory immune response in the kidney by promoting podocyte-specific expression of the stress response protein regulated in development and DNA damage response 1 (REDD1). In support of the hypothesis, streptozotocin (STZ)-induced diabetes increased REDD1 protein abundance in the kidney concomitant with renal immune cell infiltration.
View Article and Find Full Text PDFIncreasing evidence supports the role of an augmented immune response in the early development and progression of renal complications caused by diabetes. We recently demonstrated that podocyte-specific expression of stress response protein regulated in development and DNA damage response 1 (REDD1) contributes to activation of the pro-inflammatory transcription factor NF-κB in the kidney of diabetic mice. The studies here were designed to define the specific signaling events whereby REDD1 promotes NF-κB activation in the context of diabetic nephropathy.
View Article and Find Full Text PDFArticle Synopsis
- Age-related macular degeneration (AMD) is a significant cause of blindness in older adults, but the initial molecular changes that lead to vision loss are not well understood.
- Research using sodium iodate (NaIO) on mice showed increased levels of the stress response protein REDD1 in the retina, which correlates with heightened oxidative stress and inflammation when NaIO is administered.
- Mice without REDD1 experienced less damage, including reduced oxidative stress and preserved retinal structure, suggesting that REDD1 plays a crucial role in developing retinal issues associated with dry AMD.
Article Synopsis
- Activation of NF-κB in heart cells (cardiomyocytes) is linked to heart function issues in diabetes, primarily through the production of inflammatory proteins.
- The protein REDD1 is crucial for increasing these inflammatory proteins in diabetic hearts, as its absence leads to decreased NF-κB signaling and reduced expression of pro-inflammatory cytokines.
- In diabetic mice, REDD1 influences heart function by affecting GSK3β activity, with its presence linked to serious cardiac dysfunction, whereas REDD1 deficiency appears to protect against diabetes-related heart problems.
NLRP3 Inflammasome Priming in the Retina of Diabetic Mice Requires REDD1-Dependent Activation of GSK3β.
Invest Ophthalmol Vis Sci
March 2024
Article Synopsis
- This study investigates how diabetes triggers the activation of the NLRP3 inflammasome, a key player in retinal complications associated with diabetes.
- Researchers found that both NLRP3 and interleukin-1β (IL-1β) levels increased in diabetic mice and cultured Müller cells under hyperglycemic conditions, with the stress response protein REDD1 being essential for this increase.
- The findings suggest that REDD1 influences GSK3β activity, which is crucial for NLRP3 inflammasome activation and IL-1β production in Müller glial cells during diabetes, potentially affecting visual function in diabetic mice.