CFTR x Sodium-hydrogen exchangers

Insights into acute DRA regulation relevant to secretory diarrhea studied synergistic cAMP and Ca2+-induced DRA stimulation. DRA was phosphorylated under baseline conditions, which decreased with acute stimulation. Acute stimulation, but not basal activity, required the presence of both IRBIT and LIMA1 (an actin-binding scaffold), involved more plasma membrane DRA, and also increased DRA association with IRBIT and LIMA1, indicating a role for a DRA-IRBIT-LIMA1 plasma membrane complex in acute DRA stimulation.

Excessive antibiotic use can lead to gut microbiota dysbiosis, resulting in diarrhea. This study aimed to investigate the effects of Bifidobacterium animalis QC08 (QC08) on the antibiotic-induced diarrhea mouse model using lincomycin hydrochloride. Mice were divided into five groups: normal, diarrhea, a drug group, high-dose QC08 (QC08-H), low-dose QC08 (QC08-L). Compared with the diarrhea group, the QC08-H and QC08-L groups showed a decrease in serum serotonin, interleukin (IL)-17A, IL-6, and malondialdehyde levels, whereas total antioxidant capacity levels increased. In the colon and small intestine tissues of QC08-H and QC08-L treated mice, mRNA expression of cystic fibrosis transmembrane conductance regulator (CFTR), epidermal growth factor receptor (EGFR), and transforming growth factor β1 (TGFβ1) was significantly downregulated, whereas expression of sodium-hydrogen exchanger 1 (NHE1) and NHE4 was upregulated compared to the AAD model group. Altogether, this in vivo study demonstrates the potential of QC08 in alleviating AAD in mice, providing valuable insights for understanding and potentially treating antibiotic-related gut issues.

Current therapies for ADPKD involve treatment of the symptoms. A direct approach would involve a gene therapy. Here we show AAV1 is tropic for cystic epithelia, which have abundant expression of sialic acid resides known to enhance AAV1 transduction. We show that a CFTR-based vector can reduce cyst size, suggesting that it may be therapeutic. These data suggest that cysts are prime targets for AAV1 and offer an exciting prospect for ADPKD gene therapy.