Nardilysin controls cardiac sympathetic innervation patterning through regulation of p75 neurotrophin receptor

Ohno, Mikiko; Nishi, Kiyoto; Hiraoka, Yutaka; Niizuma, Shinichiro; Matsuda, Shintaro; Iwasaki, Hiromichi; Kimura, Takeshi; Nishi, Eiichiro

doi:10.1096/fj.202000604r

Cited by 5 publications

(2 citation statements)

References 58 publications

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“…We identified NRDC as a specific binding partner of HB-EGF 13 . NRDC is a multifunctional protein that enhances the ectodomain shedding of various membrane proteins in the extracellular space 14 – 19 , while it controls transcription as a co-regulator in the nucleus 20 – 23 .…”

Section: Introductionmentioning

confidence: 99%

“…However, difficulties have been associated with excluding the systemic effects of other organ-derived NRDC on BAT thermogenesis because NRDC is expressed in a wide range of tissues, including the nervous, vascular, and endocrine systems. NRDC in the peripheral nervous system may be involved in thermogenesis because the sympathetic nervous system is activated in Nrdc −/− mice 19 .…”

Section: Introductionmentioning

confidence: 99%

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Nardilysin in adipocytes regulates UCP1 expression and body temperature homeostasis

Saijo

Ohno

Iwasaki

et al. 2022

Sci Rep

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Brown adipose tissue (BAT) dissipates chemical energy as heat through uncoupling protein 1 (UCP1). The induction of mitochondrial reactive oxygen species (ROS) in BAT was recently identified as a mechanism that supports UCP1-dependent thermogenesis. We previously demonstrated that nardilysin (NRDC) plays critical roles in body temperature homeostasis. Global NRDC-deficient (Nrdc–/–) mice show hypothermia due to a lower set point for body temperature, whereas BAT thermogenesis at room temperature (RT) is enhanced mainly to compensate for poor thermal insulation. To examine the primary role of NRDC in BAT thermogenesis, we generated adipocyte-specific NRDC-deficient (Adipo-KO) mice by mating Nrdc floxed (Nrdcflox/flox) mice with adiponectin-Cre mice. Adipo-KO mice showed hyperthermia at both RT and thermoneutrality. They were also more cold-tolerant than Nrdcflox/flox mice. However, UCP1 mRNA levels were significantly lower in Adipo-KO BAT at RT, thermoneutrality, and 4 °C, whereas no significant differences were observed in UCP1 protein levels at RT and 4 °C. We examined the protein stability of UCP1 using the cycloheximide chase assay and found that NRDC negatively regulated its stability via the ubiquitin–proteasome pathway. NRDC may be also involved in ROS-mediated in vivo thermogenesis because the inhibitory effects of N-acetyl cysteine, an ROS scavenger, on β3 agonist-induced thermogenesis were stronger in Adipo-KO mice. Collectively, the present results demonstrate that NRDC in BAT controls adaptive thermogenesis and body temperature homeostasis possibly via the regulation of UCP1 protein stability and ROS levels.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nardilysin in adipocytes regulates UCP1 expression and body temperature homeostasis

Saijo

Ohno

Iwasaki

et al. 2022

Sci Rep

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Immunohistochemical and clinicopathological study regarding nardilysin on extramammary Paget's disease

et al. 2023

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Auxiliary roles of nardilysin in the early diagnosis of acute coronary syndrome: a prospective cohort study, the Nardi-ACS study

Ohno,

Shiomi,

Baba

et al. 2024

Intern Emerg Med

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Acute coronary syndrome (ACS) includes myocardial infarction (MI) and unstable angina (UA). MI is defined by elevated necrosis markers, preferably high-sensitivity cardiac troponins (hs-cTn). However, it takes hours for cTn to become elevated after coronary occlusion; therefore, difficulties are associated with diagnosing early post-onset MI or UA. The aim of this prospective cohort study was to examine the diagnostic ability of serum nardilysin (NRDC) for the early detection of ACS. This study consisted of two sequential cohorts, the Phase I cohort, 435 patients presenting to the emergency room (ER) with chest pain, and the Phase II cohort, 486 patients with chest pain who underwent coronary angiography. The final diagnosis was ACS in 155 out of 435 patients (35.6%) in the phase I and 418 out of 486 (86.0%) in the phase II cohort. Among 680 patients who presented within 24 h of onset, 466 patients (68.5%) were diagnosed with ACS. Serum NRDC levels were significantly higher in patients with ACS than in those without ACS. The sensitivity of NRDC in patients who presented within 6 h after the onset was higher than that of hsTnI, and the AUC of NRDC within 1 h of the onset was higher than that of hsTnI (0.718 versus 0.633). Among hsTnI-negative patients (300 of 680 patients: 44.1%), 136 of whom (45.3%) were diagnosed with ACS, the sensitivity and the NPV of NRDC were 73.5 and 65.7%, respectively. When measured in combination with hsTnI, NRDC plays auxiliary roles in the early diagnosis of ACS.

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Nardilysin controls cardiac sympathetic innervation patterning through regulation of p75 neurotrophin receptor

Cited by 5 publications

References 58 publications

Nardilysin in adipocytes regulates UCP1 expression and body temperature homeostasis

Nardilysin in adipocytes regulates UCP1 expression and body temperature homeostasis

Immunohistochemical and clinicopathological study regarding nardilysin on extramammary Paget's disease

Auxiliary roles of nardilysin in the early diagnosis of acute coronary syndrome: a prospective cohort study, the Nardi-ACS study

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