TRPV4 Channel Signaling in Macrophages Promotes Gastrointestinal Motility via Direct Effects on Smooth Muscle Cells

Luo, Jialie; Qian, Aihua; Oetjen, Landon K.; Yu, Weihua; Pu, Yang; Feng, Jing; Xie, Zili; Liu, Shenbin; Yin, Shen; Dryn, Dariia O.; Cheng, Jizhong; Riehl, Terrence E.; Zholos, Alexander; Stenson, William F.; Kim, Brian; Hu, Hongzhen

doi:10.1016/j.immuni.2018.04.021

Cited by 64 publications

(69 citation statements)

References 80 publications

(93 reference statements)

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“…As TRPV4 has been implicated in alveolar and intestinal macrophages (Hamanaka et al, 2010; Luo et al, 2018; Pairet et al, 2018), sensing of mechanical tissue deformation may constitute a conserved role of tissue resident macrophages throughout the body. The ability to directly interact with parenchymal cells and sensing mechanical inputs may reflect an additional division of labor between tissue resident and infiltrating monocyte-derived macrophages.…”

Section: Discussionmentioning

confidence: 99%

Resident Cardiac Macrophages Mediate Adaptive Myocardial Remodeling

Wong

Mohan

Kopecky

et al. 2021

Preprint

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SummaryCardiac macrophages represent a heterogeneous cell population with distinct origins, dynamics, and functions. Recent studies have revealed that C-C Chemokine Receptor 2 positive (CCR2+) macrophages derived from infiltrating monocytes regulate myocardial inflammation and heart failure pathogenesis. Comparatively little is known about the functions of tissue resident (CCR2−) macrophages. Herein, we identify an essential role for CCR2− macrophages in the chronically failing heart. Depletion of CCR2− macrophages in mice with dilated cardiomyopathy accelerated mortality and impaired ventricular remodeling and coronary angiogenesis, adaptive changes necessary to maintain cardiac output in the setting of reduced cardiac contractility. Mechanistically, CCR2− macrophages interacted with neighboring cardiomyocytes via focal adhesion complexes and were activated in response to mechanical stretch through a transient receptor potential vanilloid 4 (TRPV4) dependent pathway that controlled growth factor expression. These findings establish a role for tissue resident macrophages in adaptive cardiac remodeling and introduce a new mechanism of cardiac macrophage activation.

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Section: Discussionmentioning

confidence: 99%

Resident Cardiac Macrophages Mediate Adaptive Myocardial Remodeling

Wong

Mohan

Kopecky

et al. 2021

Preprint

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“…Infiltrating inflammatory cells have been shown to be in close proximity to SMC in the muscular layers and directly affect smooth muscle function by releasing pro‐inflammatory cytokines . In rats, POI decreased jejunal and colonic circular smooth contractions which are associated with decreased gastrointestinal transit linked to increasing pro‐inflammatory cytokines .…”

Section: Discussionmentioning

confidence: 99%

“…This enzyme is a key component of O 2 ‐dependent microbial activity of phagocytes that, in turn, induces muscular macrophages and polymorphonuclear neutrophil infiltration, resulting in the production of high levels of pro‐inflammatory cytokines such as tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) . Infiltrating inflammatory cells have been shown to be in close proximity to SMC in the muscularis layers and directly affect smooth muscle function by releasing pro‐inflammatory cytokines …”

Section: Introductionmentioning

confidence: 99%

Effects of electroacupuncture on the intestinal motility and local inflammation are modulated by acupoint selection and stimulation frequency in postoperative ileus mice

Yang

Tian

et al. 2020

Neurogastroenterology Motil

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Postoperative ileus (POI) is a frequent complication of abdominal surgery characterized by transient hypomotility of the gastrointestinal tract and presents as an inability to tolerate enteral nutrition, nausea, and lack of passage of flatus and stool, along with abdominal distension. 1 Acute early activation of inhibitory neural pathways and secondary late inflammatory responses are considered to be the main pathological mechanisms of POI. 2 This condition accounts for prolonged hospitalization and increased risks of aspiration and infectiousAbstract Background: Electroacupuncture (EA) is widely used in various gastrointestinal diseases around the world, including POI. Here, we investigated different therapeutic effects of EA using lower limb and abdomen acupoints. Methods: Intestinal manipulation was performed in 88 mice, and eight mice underwent a sham operation. Forty mice were randomly divided into model group and four EA groups receiving stimulation at ST36 (2, 10, 30, 100 Hz). The most effective frequency was then used in the following experiments. Forty-eight mice were randomly divided into six groups receiving EA treatment at ST37, ST39, ST25, CV4, CV12, and a non-acupuncture point. Gastrointestinal motility and plasma TNF-α, IL-6 were evaluated in all mice. The local immune response and α-smooth muscle actin (α-SMA) expression were assessed by immunofluorescence, ELISA, and HE staining.Results: ST36 stimulated with 10 or 30 Hz EA significantly increased the gastrointestinal motility and attenuated peripheral inflammation; however, ST36 stimulated with 2 or 100 Hz did not induce any effect. The therapeutic effects on motility and inflammation of 10 Hz EA in the ST36 group were similar in the ST36, ST37, ST39, or CV4 groups, but when applied to ST25, CV12 or non-acupoint had no significant differences. EA at ST36, ST37, ST39, or CV4 significantly inhibited local MPO activity, immune cells infiltration, and increased α-SMA.Conclusions: EA at lower limb and abdomen acupoints with the same stimulation parameters had different therapeutic effects on postoperative dysmotility and inflammation. Furthermore, EA protected SMC to improve gastrointestinal transit by reducing local inflammation in the intestinal musculature in POI. K E Y W O R D Sacupoints, gastrointestinal motility, myeloperoxidase, α-SMA

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“…In addition to their interaction with neurons, it was recently demonstrated that muscularis macrophages can directly interact with smooth muscle cells via TRPV4-mediated release of prostaglandin E2, affecting colonic motility. 82 Indeed, Trpv4-floxed mice showed significant reduction in colonic contraction upon treatment with GSK101, a TRPV4 channel agonist, an effect which was independent from neuronal input. These findings highlight that muscularis macrophages can also directly influence smooth muscle cells without input from the ENS.…”

Section: Muscularis Macrophagesmentioning

confidence: 98%

Intestinal resident macrophages: Multitaskers of the gut

Viola

Boeckxstaens

2020

Neurogastroenterology Motil

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Background Intestinal resident macrophages play a crucial role in homeostasis and have been implicated in numerous gastrointestinal diseases. While historically believed to be largely of hematopoietic origin, recent advances in fate‐mapping technology have unveiled the existence of long‐lived, self‐maintaining populations located in specific niches throughout the gut wall. Furthermore, the advent of single‐cell technology has enabled an unprecedented characterization of the functional specialization of tissue‐resident macrophages throughout the gastrointestinal tract. Purpose The purpose of this review was to provide a panorama on intestinal resident macrophages, with particular focus to the recent advances in the field. Here, we discuss the functions and phenotype of intestinal resident macrophages and, where possible, the functional specialization of these cells in response to the niche they occupy. Furthermore, we will discuss their role in gastrointestinal diseases.

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TRPV4 Channel Signaling in Macrophages Promotes Gastrointestinal Motility via Direct Effects on Smooth Muscle Cells

Cited by 64 publications

References 80 publications

Resident Cardiac Macrophages Mediate Adaptive Myocardial Remodeling

Resident Cardiac Macrophages Mediate Adaptive Myocardial Remodeling

Effects of electroacupuncture on the intestinal motility and local inflammation are modulated by acupoint selection and stimulation frequency in postoperative ileus mice

Intestinal resident macrophages: Multitaskers of the gut

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