rat-animal-models-for-evaluation-effects-sacral-peripheral-nerve

Rat Animal Models for Evaluation of the Effects of Sacral and Peripheral Nerve Stimulation on Bladder Function

Neuromodulation, a therapeutic approach to the dysfunction of various organs, has proven effective in treating lower urinary tract dysfunctions. Despite ...

University of Southern Denmark

Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein belonging to the fibrinogen-related domain family. It has been localized to elastic fiber-rich regions in several tissues including the arteries, lungs, heart and skin. MFAP4 binds collagen, fibrillins and tropoelastin and contributes to the process of microfibrillar assembly and maturation of elastic fibers. MFAP4 can also bind RGD-dependent integrins, predominantly αβ and αβ through its N-terminal RGD sequence, modulating cellular behavior. Circulating MFAP4 was suggested as a robust biomarker for hepatitis C virus- and alcoholic liver disease-related liver fibrosis, cardiovascular disorders and chronic obstructive pulmonary disease. In mice, MFAP4 seems to have a widely redundant role under homeostatic conditions, as global MFAP4 deficiency results in a mild pulmonary phenotype, causing emphysema-like airspace enlargement that progresses with age. However, emerging in vivo and in vitro data suggest that MFAP4 is actively involved in the pathogenesis of remodeling-associated diseases, including fibrosis, cardiovascular disorders, aging, asthma and cancer through activation of integrin-mediated signaling as well as by modulating TGF-β pathway, thus supporting maladaptive matrix remodeling. This review summarizes the current knowledge about MFAP4 structure and localization, its mechanisms of action in disease-induced tissue remodeling as well as its potential role as a clinical biomarker.

Microfibrillar-associated protein 4 in health and disease.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in different countries. Liver fibrosis is considered as the most appropriate predictor of NAFLD-associated outcome. Microfibrillar-associated protein 4 (MFAP4) is a glycoprotein located in the extracellular matrix. Circulatory MFAP4 has been suggested as a noninvasive biomarker for the assessment of hepatitis C virus and alcoholic liver disease associated liver fibrosis. In this study, we aimed to investigate the association between serum MFAP4 and liver fibrosis severity in NAFLD patients.

Serum MFAP4, a novel potential biomarker for liver cirrhosis screening, correlates with transient elastography in NAFLD patients.

Neuromodulation has been used in the treatment of various pelvic organ dysfunctions for almost 40 years and several placebo-controlled studies have confirmed its clinical effect. Many neuromodulation methods using different devices and stimulation parameters, targeting different neural structures have been introduced, but only a limited number have been adopted into routine clinical use. A substantial volume of basic research and clinical studies addressing specific effects of neuromodulation in the treatment of overactive bladder (OAB) have been published to date; however, their mechanistic implications have not been comprehensively summarized. Thus, our understanding of the mechanism of action of neuromodulation in OAB treatment is mainly based on postulated theories. Results from animal experiments suggest that different neuromodulation methods used to treat OAB share the same basic principles. The most likely explanation for the effect of neuromodulation in OAB therapy is the suppression of bladder afferent signalling, promotion of spinal guarding reflexes and modulation of non-specific supraspinal regulatory circuits.

Article	Year
Microfibrillar-associated protein 4 in health and disease. Matrix biology : journal of the International Society for Matrix Biology\| PubMed ID: 35644509	2022
Serum MFAP4, a novel potential biomarker for liver cirrhosis screening, correlates with transient elastography in NAFLD patients. JGH open : an open access journal of gastroenterology and hepatology\| PubMed ID: 36968563	2023
The mechanism of action of neuromodulation in the treatment of overactive bladder. Nature reviews. Urology\| PubMed ID: 39653756	2025

Reine Kanaan

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