Abstract
Intractable gastrointestinal (GI) diseases often develop during infancy. Our group previously reported that natriuretic peptide receptor B (NPR-B)-deficient Npr2slw/slw mice exhibit severe intestinal dysfunction, such as stenosis and distention, which resembles the dysfunction observed in Hirschsprung’s disease-allied disorders. However, the root cause of intestinal dysfunction and the detailed of pathophysiological condition in the intestine are not yet clear. Here, we report that the intestine of preweaning Npr2slw/slw mice showed bloodless blood vessels, and nodes were found in the lymphatic vessel. Additionally, the lacteals, smooth muscle, blood vessel, and nerves were barely observed in the villi of preweaning Npr2slw/slw mice. Moreover, intramuscular interstitial cells of Cajal (ICC-IM) were clearly reduced. In contrast, villi and ICC-IM were developed normally in surviving adult Npr2slw/slw mice. However, adult Npr2slw/slw mice exhibited partially hypoplastic blood vessels and an atrophied enteric nervous. Furthermore, adult Npr2slw/slw mice showed markedly reduced white adipose tissue. These findings suggest that the cause of GI dysfunction in preweaning Npr2slw/slw mice is attributed to defective intestinal development with microcirculation disorder. Thus, it is suggested that NPR-B signaling is involved in intestinal development and control of microcirculation and fat metabolism. This report provides new insights into intractable GI diseases, obesity, and NPR-B signaling.
Highlights
Intractable gastrointestinal (GI) diseases often develop during infancy
Small nodes were observed in lymphatic vessels, and LYVE-1-positive macrophages were slightly larger in Npr2slw/slw mice than in control mice (Fig. 1b iv)
In some cases, Npr2slw/slw mice showed cobweb-like microtubular structures filled with Oil Red-O stained microgranules (Supplementary Fig. 2c and d)
Summary
Intractable gastrointestinal (GI) diseases often develop during infancy. Our group previously reported that natriuretic peptide receptor B (NPR-B)-deficient Npr2slw/slw mice exhibit severe intestinal dysfunction, such as stenosis and distention, which resembles the dysfunction observed in Hirschsprung’s disease-allied disorders. Adult Npr2slw/slw mice showed markedly reduced white adipose tissue These findings suggest that the cause of GI dysfunction in preweaning Npr2slw/slw mice is attributed to defective intestinal development with microcirculation disorder. In patients with Hirschsprung’s disease-allied disorders (HDAD)[5,6,7], the ENS is present, yet distension and/or stenosis develop, causing reduced GI motility, a decline in GI transit, and excretory d isorders[8,9]. These defects lead to bacterial growth, resulting in enteritis and sepsis. These observations indicate the important role of NPR-B in the physiological functions of the GI tract
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