Insights on gastrointestinal motility through the use of optogenetic sensors and actuators

Drumm, Bernard T.; Cobine, Caroline A.; Baker, Salah A.

doi:10.1113/jp281930

Cited by 10 publications

(3 citation statements)

References 197 publications

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“…These findings, together with our study, suggest that miR‐10b deficiency leads to intestinal permeability, dysregulation of tight junctions, and gut immune dysfunction. Additionally, it is of paramount importance to uncover the role of miR‐10b‐5p in other cells essential to proper gut function and maintenance, such as neurons, PDGFRα cells, smooth muscle cells, etc 55–60 . Furthermore, the leaky gut phenotype should be assessed using an Ussing chamber, which is currently the gold standard for measuring epithelial barrier permeability.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, it is of paramount importance to uncover the role of miR‐10b‐5p in other cells essential to proper gut function and maintenance, such as neurons, PDGFRα cells, smooth muscle cells, etc. 55 , 56 , 57 , 58 , 59 , 60 Furthermore, the leaky gut phenotype should be assessed using an Ussing chamber, which is currently the gold standard for measuring epithelial barrier permeability. Moreover, the validation of the leaky gut phenotype should be conducted using a larger number of patients.…”

Section: Discussionmentioning

confidence: 99%

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miR‐10b‐5p rescues leaky gut linked with gastrointestinal dysmotility and diabetes

Zogg,

Singh,

et al. 2023

UEG Journal

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Background/AimDiabetes has substantive co‐occurrence with disorders of gut‐brain interactions (DGBIs). The pathophysiological and molecular mechanisms linking diabetes and DGBIs are unclear. MicroRNAs (miRNAs) are key regulators of diabetes and gut dysmotility. We investigated whether impaired gut barrier function is regulated by a key miRNA, miR‐10b‐5p, linking diabetes and gut dysmotility.MethodsWe created a new mouse line using the Mb3Cas12a/Mb3Cpf1 endonuclease to delete mir‐10b globally. Loss of function studies in the mir‐10b knockout (KO) mice were conducted to characterize diabetes, gut dysmotility, and gut barrier dysfunction phenotypes in these mice. Gain of function studies were conducted by injecting these mir‐10b KO mice with a miR‐10b‐5p mimic. Further, we performed miRNA‐sequencing analysis from colonic mucosa from mir‐10b KO, wild type, and miR‐10b‐5p mimic injected mice to confirm (1) deficiency of miR‐10b‐5p in KO mice, and (2) restoration of miR‐10b‐5p after the mimic injection.ResultsCongenital loss of mir‐10b in mice led to the development of hyperglycemia, gut dysmotility, and gut barrier dysfunction. Gut permeability was increased, but expression of the tight junction protein Zonula occludens‐1 was reduced in the colon of mir‐10b KO mice. Patients with diabetes or constipation‐ predominant irritable bowel syndrome, a known DGBI that is linked to leaky gut, had significantly reduced miR‐10b‐5p expression. Injection of a miR‐10b‐5p mimic in mir‐10b KO mice rescued these molecular alterations and phenotypes.ConclusionsOur study uncovered a potential pathophysiologic mechanism of gut barrier dysfunction that links both the diabetes and gut dysmotility phenotypes in mice lacking miR‐10b‐5p. Treatment with a miR‐10b‐5p mimic reversed the leaky gut, diabetic, and gut dysmotility phenotypes, highlighting the translational potential of the miR‐10b‐5p mimic.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

miR‐10b‐5p rescues leaky gut linked with gastrointestinal dysmotility and diabetes

Zogg,

Singh,

et al. 2023

UEG Journal

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“…ICC are rich in multiple organelles, including numerous mitochondria and abundant endoplasmic reticula (41). With a highly branched morphology and cellular network, ICC are an important component of the gastrointestinal tract (42). Additional evidence has shown that ICC contribute to intestinal motility by generating spontaneous electrical depolarization and increasing smooth muscle excitability (43).…”

Section: Discussionmentioning

confidence: 99%

Arctiin alleviates functional constipation by enhancing intestinal motility in mice

et al. 2023

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Interstitial cell of Cajal-like cells (ICC-LC) exhibit dynamic spontaneous activity but are not functionally innervated in mouse urethra

Gupta,

Baker,

Sanders

et al. 2024

Cell Calcium

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Insights on gastrointestinal motility through the use of optogenetic sensors and actuators

Abstract: support-information-section).

Cited by 10 publications

References 197 publications

miR‐10b‐5p rescues leaky gut linked with gastrointestinal dysmotility and diabetes

miR‐10b‐5p rescues leaky gut linked with gastrointestinal dysmotility and diabetes

Arctiin alleviates functional constipation by enhancing intestinal motility in mice

Interstitial cell of Cajal-like cells (ICC-LC) exhibit dynamic spontaneous activity but are not functionally innervated in mouse urethra

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