Impact of hyperoxaluria on kidney stone modulating glycoproteins and endoplasmic reticulum stress in the renal tissue of rats

Abstract

Till date researchers have emphasized the structural alteration in urinary glycoproteins as a perpetrator in renal stone formation, however, data portraying the inter-linkage between the glycoproteins and role of endoplasmic reticulum (ER) is lacking. The present study therefore, has accentuated the influence of hyperoxaluria on urinary glycoproteins, chaperone and ER. The revelations depicted escalated expression of osteopontin and calnexin which suggests their involvement in incurring renal damage. However, expression of THP remained unaltered, but depicted a change in its structural conformation. Further, the evoking of ER stress cemented the ER involvement in the pathogenesis of renal stones. Also, the hampered calcium homeostasis along with elevated protein aggregation was observed. These findings highlight the central involvement of ER in modulating the renal stone formation. Deployment of 4-PBA, an ER stress inhibitor showcased the potential of being an effective therapeutic as evident by the normalised levels of osteopontin, calnexin, however THP exhibited no change. The reduction in calcium oxalate crystals deposition and normalization ofrenalhistoarchitecture indicates towards the efficacy of 4-PBA. The extentof ER stress and compromised protein folding was ameliorated post 4-PBA treatment. 4-PBA led curbing of ER stress exhibited a restoration of compromised mitochondrial functioning along with diminished oxidative stress. 4-PBA plausibly restored the calcium homeostasis, inflammation and apoptosis. A putative inter- communication of ER and mitochondria along with their rehabilitation via 4-PBA was delineated. Therefore, suggesting the major role of ER in hyperoxaluric manifestations thereby providing an opportunity to target ER stress for future therapeuticinterventions.