Expression of ALMS1 in podocytes: possible role in filtration function.

Previously, we identified Alstrom Syndrome 1 (ALMS1) as an interacting partner of NKCC2 in the Thick Ascending limb of the loop of Henle (TAL). Mutations in the ALMS1 gene in humans cause Alström syndrome, characterized by progressive metabolic alterations that include obesity, hypertension, and chronic kidney disease (CDK). SNPs in ALMS1 are associated with lower GFR in GWAS. However, role of ALMS1 in glomerular filtration has not been studied. We hypothesized that ALMS1 is expressed in glomerular podocytes where it may play a role in podocyte filtration function. To begin studying this, we localized ALMS1 expression to podocytes by immunofluorescence labeling of Actinin-4, abundantly expressed in podocytes, and ALMS1. Confocal imaging showed that ALMS1 is co-localized with Actinin-4 in rat podocytes. In addition, ALMS1 was also expressed in an immortalized mouse podocyte cell line, as was Actinin-4 and nephrin, as measured by Western blot and immunofluorescence microscopy. To determine if ALMS1 plays a role in podocyte pathology we measured nephrin expression in ALMS1 KO rats. These rats were generated in the Dahl SS genetic background and are hypertensive on a normal salt diet. We found that nephrin expression in renal cortical lysates was decreased by 61±08% (p<0.05, n=7) in ALMS1 KO rats. To study if ALMS1 deletion could play a role in filtration barrier function we measured albumin/creatinine ratio in urine samples from 14-16 weeks old wild type (WT) and ALMS1 KO rats. In ALMS1 KO rats, urinary albumin excretion was higher than control rats (WT: 4±2; ALMS1 KO: 26±6, n=6, p<0.05). Taken together, our data show that ALMS1 is expressed in rat and mouse podocytes where it may play a role in filtration barrier function by maintaining podocyte biology. © FASEB.

Citation

Dipak Maskey, Ankita Jayakumar, Sumit R Monu, Pablo A Ortiz. Expression of ALMS1 in podocytes: possible role in filtration function. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2022 May;36 Suppl 1

PMID: 35553156

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