{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough none of the abstracts explicitly mention MIR6852, the body of work on bestrophin proteins suggests that MIR6852 may impact a family of Ca2+-dependent anion channels that are crucial for maintaining epithelial ion homeostasis. In particular, studies on bestrophin genes indicate that these channels mediate the transport of both Cl⁻ and HCO3⁻, with mutations in bestrophin‐1 significantly disrupting anion flux across the retinal pigment epithelium—a defect that may underlie several retinal pathologies. Disruption of bestrophin‐2 has also been characterized in murine models, underscoring its essential physiological role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "Dissection of the channel’s biophysical properties has revealed that the Asp‐rich domain in bestrophins is critical for Ca2+ binding and subsequent activation of the Cl⁻ current. In airway epithelia, both bestrophin‐1 and bestrophin‐2 contribute to Ca2+-activated Cl⁻ secretion, as evidenced by reduced currents when one or both paralogs are absent or knocked down. This molecular insight into Ca2+ regulation offers a mechanistic explanation for altered anion secretion observed in disease contexts such as cystic fibrosis and other disorders linked to dysregulated ion transport."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "In other epithelial systems, the role of bestrophin channels extends to the regulation of bicarbonate transport. In the colonic mucosa, bestrophin‐2, localized basolaterally in goblet cells, appears to be pivotal for cholinergically stimulated HCO3⁻ secretion—suggesting an unanticipated role in modulating luminal pH and hydration. Moreover, in the olfactory neuroepithelium, bestrophin‐2 expression is associated with the differentiation of sensory neurons and the maturation of their cilia, which are imperative for odorant detection. Collectively, these findings imply that if MIR6852 influences bestrophin expression or function, it may impact diverse physiological processes by modulating Ca2+-dependent Cl⁻ and HCO3⁻ fluxes across multiple tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Benjamin Bakall, Precious McLaughlin, J Brett Stanton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bestrophin-2 is involved in the generation of intraocular pressure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.07-1338"}], "href": "https://doi.org/10.1167/iovs.07-1338"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18385076"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18385076"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhiqiang Qu, H Criss Hartzell "}, {"type": "b", "children": [{"type": "t", "text": "Bestrophin Cl- channels are highly permeable to HCO3-."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00398.2007"}], "href": "https://doi.org/10.1152/ajpcell.00398.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18400985"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18400985"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "René Barro-Soria, Rainer Schreiber, Karl Kunzelmann "}, {"type": "b", "children": [{"type": "t", "text": "Bestrophin 1 and 2 are components of the Ca(2+) activated Cl(-) conductance in mouse airways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2008.06.016"}], "href": "https://doi.org/10.1016/j.bbamcr.2008.06.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18652850"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18652850"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Agata Kranjc, Federico W Grillo, Juraj Rievaj, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of bestrophins by Ca2+: a theoretical and experimental study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0004672"}], "href": "https://doi.org/10.1371/journal.pone.0004672"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19262692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19262692"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Daniel Klimmeck, Philipp C Daiber, Anja Brühl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bestrophin 2: an anion channel associated with neurogenesis in chemosensory systems."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Comp Neurol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cne.22075"}], "href": "https://doi.org/10.1002/cne.22075"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19480000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19480000"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kuai Yu, Rafael Lujan, Alan Marmorstein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bestrophin-2 mediates bicarbonate transport by goblet cells in mouse colon."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI41129"}], "href": "https://doi.org/10.1172/JCI41129"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20407206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20407206"}]}]}]}