Th17 Cell-Derived Amphiregulin Promotes Colitis-Associated Intestinal Fibrosis Through Activation of mTOR and MEK in Intestinal Myofibroblasts

Zhao, Xiaojing; Yang, Wenjing; Yu, Tianxiang; Yu, Yu; Cui, Xiufang; Zhou, Zheng; Yang, Hui; Yu, Yanbo; Bilotta, Anthony J.; Yao, Suxia; Xu, Jimin; Zhou, Jia; Yochum, Gregory S.; Koltun, Walter A.; Portolese, Austin; Zeng, Defu; Xie, Jingwu; Pinchuk, Iryna V.; Zhang, Hongjie; Cong, Yingzi

doi:10.1053/j.gastro.2022.09.006

Cited by 35 publications

(29 citation statements)

References 39 publications

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“…In contrast, inhibiting the infiltration and differentiation of T H 1 and Th17 cells alleviates the development of inflammation in the colitis model, indicating a pathogenic role of Th17 cells in the intestinal lamina propria [ 67 , 68 ]. Th17 cell-driven proteins also aggravate intestinal fibrosis in a colitis model, indicating a more severe stage of inflammation [ 69 ]. Given the pathogenicity of Th17 cells in colitis, it is remarkable that several natural herbs can effectively diminish the frequency of Th17 cells in the intestine [ 42 , 70 ].…”

Section: Discussionmentioning

confidence: 99%

Biometabolites of Citrus unshiu Peel Enhance Intestinal Permeability and Alter Gut Commensal Bacteria

Lee

Seo²,

Lee³

et al. 2023

Nutrients

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Flavanones in Citrus unshiu peel (CUP) have been used as therapeutic agents to reduce intestinal inflammation; however, the anti-inflammatory effects of their biometabolites remain ambiguous. Here, we identified aglycone-type flavanones, such as hesperetin and naringenin, which were more abundant in the bioconversion of the CUP than in the ethanol extracts of the CUP. We found that the bioconversion of the CUP induced the canonical nuclear factor-κB pathway via degradation of IκB in Caco-2 cells. To check the immune suppressive capacity of the aglycones of the CUP in vivo, we orally administered the bioconversion of the CUP (500 mg/kg) to mice for two weeks prior to the 3% dextran sulfate sodium treatment. The CUP-pretreated group showed improved body weight loss, colon length shortage, and intestinal inflammation than the control mice. We also found a significant decrease in the population of lamina propria Th17 cells in the CUP-pretreated group following dextran sodium sulfate (DSS) treatment and an increase in mRNA levels of occludin in CUP-treated Caco-2 cells. Pyrosequencing analysis revealed a decreased abundance of Alistipes putredinis and an increased abundance of Muribaculum intestinale in the feces of the CUP-pretreated mice compared to those of the control mice. Overall, these findings suggest that the pre-administration of CUP biometabolites may inhibit the development of murine colitis by modulating intestinal permeability and the gut microbiome.

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Section: Discussionmentioning

confidence: 99%

Biometabolites of Citrus unshiu Peel Enhance Intestinal Permeability and Alter Gut Commensal Bacteria

Lee

Seo²,

Lee³

et al. 2023

Nutrients

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“…Fibroblasts have long been recognized as an important source of myofibroblasts which are considered the chief effector cell in fibrogenesis 47 . Considering the important roles of these cells in the occurrence and development of intestinal fibrosis, myofibroblast‐ and fibroblast‐based anti‐fibrotic strategies have been widely investigated (Table 2).…”

Section: Intestinal Fibrosismentioning

confidence: 99%

Prospective therapeutics for intestinal and hepatic fibrosis

Zhao

et al. 2023

Bioengineering & Transla Med

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Currently, there are no effective therapies for intestinal and hepatic fibrosis representing a considerable unmet need. Breakthroughs in pathogenesis have accelerated the development of anti‐fibrotic therapeutics in recent years. Particularly, with the development of nanotechnology, the harsh environment of the gastrointestinal tract and inaccessible microenvironment of fibrotic lesions seem to be no longer considered a great barrier to the use of anti‐fibrotic drugs. In this review, we comprehensively summarize recent preclinical and clinical studies on intestinal and hepatic fibrosis. It is found that the targets for preclinical studies on intestinal fibrosis is varied, which could be divided into molecular, cellular, and tissues level, although little clinical trials are ongoing. Liver fibrosis clinical trials have focused on improving metabolic disorders, preventing the activation and proliferation of hepatic stellate cells, promoting the degradation of collagen, and reducing inflammation and cell death. At the preclinical stage, the therapeutic strategies have focused on drug targets and delivery systems. At last, promising remedies to the current challenges are based on multi‐modal synergistic and targeted delivery therapies through mesenchymal stem cells, nanotechnology, and gut‐liver axis providing useful insights into anti‐fibrotic strategies for clinical use.

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“…Over 100 original clinical and scientific research articles have been published using these specimens. These publications have been the result of work with more than 30 collaborating scientists and relate to the genetics and pathophysiology diverticulitis, 31,32 the genetic basis of IBD, 33,34 disease phenotype/ genotype correlations, [35][36][37] mucus defense, 38,39 bowel permeability and myofibroblast function in IBD, [40][41][42][43] and colorectal cancer. 44,45…”

Section: The Hmc Carlino Family Ibcrd Biobank History and Settingmentioning

confidence: 99%

Creating a Surgical Biobank: The Hershey Medical Center Experience

Mankarious

Connelly

Harris

et al. 2023

Diseases of the Colon &Amp; Rectum

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BACKGROUND: Tissue harvesting at the time of surgery offers surgeons and scientists a unique opportunity to discover and better understand disease pathophysiology. Tissue biobanking presents challenges in patient consents, specimen collection, preparation, and storage, but the potential for scientific discovery justifies the effort. Although the number of tissue biobanks is increasing worldwide, information regarding necessary infrastructure, process flow, and management of expected obstacles is lacking. OBJECTIVE: To provide a framework and motivation for clinician scientists intending to start an intestinal tissue biobank under their direction. DATA SOURCES: The Carlino Family Inflammatory Bowel and Colorectal Diseases Biobank is housed at the Milton S. Hershey Medical Center. STUDY SELECTION: Review. INTERVENTION: Implementation of a surgical tissue biobank at a large tertiary care institution. MAIN OUTCOME MEASURES: Assess critical challenges and obstacles over the years as well as keys to the success of the program. RESULTS: Over 2 decades, the institutional biobank grew from an IBD biobank to one which now incorporates thousands of surgical specimens representing numerous colorectal diseases. This was done through a process of refinement focusing on patient recruitment and an efficient consenting and specimen management process. The biobank’s success is further insured by institutional, external, and philanthropic support; scientific collaborations; and sharing of biological specimens with other groups of dedicated researchers. LIMITATIONS: This is a single-center experience in collecting surgically resected colorectal specimens. CONCLUSIONS: Surgical specimen biobanks are essential in studying disease cause using genomics, transcriptomics, and proteomic technologies. Therefore, surgeons, clinicians, and scientists should build biobanks at their institutions to promote further scientific discovery and improve specimen diversity.

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Th17 Cell-Derived Amphiregulin Promotes Colitis-Associated Intestinal Fibrosis Through Activation of mTOR and MEK in Intestinal Myofibroblasts

Cited by 35 publications

References 39 publications

Biometabolites of Citrus unshiu Peel Enhance Intestinal Permeability and Alter Gut Commensal Bacteria

Biometabolites of Citrus unshiu Peel Enhance Intestinal Permeability and Alter Gut Commensal Bacteria

Prospective therapeutics for intestinal and hepatic fibrosis

Creating a Surgical Biobank: The Hershey Medical Center Experience

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