Hydroxychloroquine ameliorates immune functionality and intestinal flora disorders of IgA nephropathy by inhibition of C1GALT1/Cosmc pathway.

BACKGROUND

Hydroxychloroquine (HCQ) has emerged as a potential and secure antiproteinuric agent in IgA nephropathy (IgAN). This study endeavored to explore the impact of HCQ on the immune functionality and intestinal flora disorders in IgAN rats, as well as to elucidate the underlying mechanisms through and experiments.

METHODS

IgAN model was established in Sprague-Dawley rats through the administration of BSA, LPS, and CCl, and the IgAN rats received a continuous 8-week treatment with HCQ. Moreover, the human glomerular mesangial cells (HMCs) were incubated with IgA1 to establish an cellular model of IgAN. At the end of experimental period, samples were collected for further analysis.

RESULTS

HCQ ameliorated the elevated levels of 24hUTP, SCr, BUN, the number of urinary RBC, and the activation of inflammation-related proteins within the TLR4/NF-κB signaling pathway. In the IgAN rat group, there was a pronounced escalation in IgA deposition, mesangial matrix hyperplasia, and glomerular inflammatory cell infiltration, while the administration of HCQ effectively mitigated these pathological changes. In addition, the reduced production of CD4CD25Foxp3 Treg in the IgAN group was effectively reversed by HCQ. Furthermore, HCQ has the capacity to restore the compromised state of the intestinal mucosal barrier induced by IgAN and mitigate the circumstances of intestinal permeability and disruption in the intestinal flora.

CONCLUSION

HCQ diminishes IgA aberrant glycosylation levels, ameliorates renal and intestinal histopathological damage, and attenuates intestinal flora disorders and immune dysfunction in IgAN rats by means of activating the C1GALT1/Cosmc pathway.