{"title":"New Insights into the Pathogenesis of Diabetic Nephropathy: Proximal Renal Tubules Are Primary Target of Oxidative Stress in Diabetic Kidney.","authors":"Ryuma Haraguchi, Yukihiro Kohara, Kanako Matsubayashi, Riko Kitazawa, Sohei Kitazawa","doi":"10.1267/ahc.20008","DOIUrl":"https://doi.org/10.1267/ahc.20008","url":null,"abstract":"<p><p>Diabetic nephropathy is a major source of end-stage renal failure, affecting about one-third cases of diabetes mellitus. It has long been accepted that diabetic nephropathy is mainly characterized by glomerular defects, while clinical observations have implied that renal tubular damage is closely linked to kidney dysfunction at the early stages of diabetic nephropathy. In this study, we conducted pathohistological analyses focusing on renal tubular lesions in the early-stage diabetic kidney with the use of a streptozotocin (STZ)-induced diabetes mellitus mouse model. The results revealed that histological alterations in renal tubules, shown by a vacuolar nucleic structure, accumulations of PAS-positive substance, and accelerated restoration stress, occur initially without the presence of glomerular lesions in the early-stage diabetic kidney, and that these tubular defects are localized mainly in proximal renal tubules. Moreover, enhanced expression of RAGE, suggesting an aberrant activation of AGEs-RAGE signaling pathway, and accumulation of oxidative modified mitochondria through the impaired autophagy/lysosome system, were also seen in the damaged diabetic proximal renal tubules. Our findings indicate that proximal tubular defects are the initial pathological events increasingly linked to the progression of diabetic nephropathy, and that controlling renal tubular damage could be an effective therapeutic strategy for the clinical treatment of diabetic nephropathy.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"53 2","pages":"21-31"},"PeriodicalIF":2.4,"publicationDate":"2020-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1267/ahc.20008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37936912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kenta Masui, Mio Harachi, Webster K Cavenee, Paul S Mischel, Noriyuki Shibata
{"title":"Codependency of Metabolism and Epigenetics Drives Cancer Progression: A Review.","authors":"Kenta Masui, Mio Harachi, Webster K Cavenee, Paul S Mischel, Noriyuki Shibata","doi":"10.1267/ahc.20002","DOIUrl":"10.1267/ahc.20002","url":null,"abstract":"<p><p>Cancer is widely considered to be a set of genetic diseases that are currently classified by tissue and cell type of origin and, increasingly, by its molecular characteristics. This latter aspect is based primarily upon oncogene gains, tumor suppressor losses, and associated transcriptional profiles. However, cancers are also characterized by profound alterations in cellular metabolism and epigenetic landscape. It is particularly noteworthy that cancer-causing genomic defects not only activate cell cycle progression, but regulate the opportunistic uptake and utilization of nutrients, effectively enabling tumors to maximize growth and drug resistance in changing tissue and systemic microenvironments. Shifts in chromatin architecture are central to this dynamic behavior. Further, changes in nutrient uptake and utilization directly affect chromatin structure. In this review, we describe a set of recent discoveries of metabolic and epigenetic reprogramming in cancer, and especially focus on the genomically well-characterized brain tumor, glioblastoma. Further, we discuss a new mode of metabolic regulation driven by epigenetic mechanisms, that enables cancer cells to autonomously activate iron metabolism for their survival. Together, these underscore the integration of genetic mutations with metabolic reprogramming and epigenetic shifts in cancer, suggesting a new means to identifying patient subsets suitable for specific precision therapeutics.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"53 1","pages":"1-10"},"PeriodicalIF":2.4,"publicationDate":"2020-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37762132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Incremental Growth Lines in Mouse Molar Dentin Represent 8-hr Ultradian Rhythm.","authors":"Ryutaro Ono, Nobuya Koike, Hitoshi Inokawa, Yoshiki Tsuchiya, Yasuhiro Umemura, Toshiro Yamamoto, Narisato Kanamura, Kazuhiro Yagita","doi":"10.1267/ahc.19017","DOIUrl":"https://doi.org/10.1267/ahc.19017","url":null,"abstract":"<p><p>Rhythmic incremental growth lines occur in dental hard tissues of vertebrates, and dentinogenesis in rodent incisors is suggested to be controlled by the 24-hr circadian clock. Rodent incisors continue to grow throughout the animal's life; however, similar to human teeth, rodent molars stop growing after crown formation. This similarity suggests that the mouse molar is an excellent model to understand the molecular mechanisms underlying growth of human teeth. However, not much is known about the rhythmic dentinogenesis in mouse molars. Here, we investigated the incremental growth lines in mouse molar dentin using tetracycline as the growth marker. The incremental growth lines were observed to be generated at approximately 8-hr intervals in wild-type mice housed under 12:12 hr light-dark conditions. Moreover, the 8-hr rhythmic increments persisted in the wild-type and <i>Bmal1<sup>-/-</sup></i> mice housed in constant darkness, where <i>Bmal1<sup>-/-</sup></i> mice become behaviorally arrhythmic. These results revealed that the dentinogenesis in mouse molars underlie the ultradian rhythms with around 8-hr periodicity. Further, the circadian clock does not seem to be involved in this process, providing new insight into the mechanisms involved in the tooth growth.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"52 6","pages":"93-99"},"PeriodicalIF":2.4,"publicationDate":"2019-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1267/ahc.19017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37594548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Localization and Accumulation Studies of Dacomitinib in Rat Intestines and Skin by Immunohistochemistry.","authors":"Yutaro Yamamoto, Tetsuya Saita, Asuki Oka, Hiroto Kataoka, Masashi Shin","doi":"10.1267/ahc.19031","DOIUrl":"https://doi.org/10.1267/ahc.19031","url":null,"abstract":"<p><p>Dacomitinib, a second-generation tyrosine kinase inhibitor, was irreversible inhibitor forming covalent bonds with the kinase domains of EGFR and other ErbB family receptors. Dacomitinib has been approved for the treatment of locally advanced or metastatic non-small cell lung cancer. In this study, we aimed to develop an immunohistochemistry to detect dacomitinib-ErbB family receptor conjugates. Immunostaining was performed in rat intestine and skin tissues after oral administration of dacomitinib. Following a single oral dose of dacomitinib, strong staining was observed after 24 hr in the ileum and colon, with only slight staining in the duodenum and jejunum. In the skin, strong staining was observed in the epidermis, hair follicles, and sebaceous glands. Moreover, significant amounts of dacomitinib remained for up to 72 hr post-administration in the ileum, colon, and skin. This report is the first to elucidate the localization and accumulation of dacomitinib in the rat intestine and skin and should be valuable during efforts to clarify the mechanism dacomitinib-induced diarrhea or skin toxicities.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"52 6","pages":"101-106"},"PeriodicalIF":2.4,"publicationDate":"2019-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1267/ahc.19031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37594549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hypothalamic Kisspeptin Expression in Hyperandrogenic Female Rats and Aging Rats","authors":"K. Iwata, Yuyu Kunimura, H. Ozawa","doi":"10.1267/ahc.19013","DOIUrl":"https://doi.org/10.1267/ahc.19013","url":null,"abstract":"Hypothalamic kisspeptin neurons stimulate gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) release. Kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) of rats induce an LH surge for ovulation, and those in the arcuate nucleus (ARC) regulate pulsatile LH secretion for follicle development and spermatogenesis. Dysfunction of kisspeptin neurons thus reduces the reproductive function. This review focuses on the effect of androgen or aging on kisspeptin expression in rats. Although androgen directly suppresses ARC kisspeptin neurons in female rats, the AVPV kisspeptin neurons are hardly affected. In rats, plasma LH concentrations decrease in both sexes with aging, and ARC kisspeptin expression also decreases in old rats compared with young rats. In addition, kisspeptin neurons may be associated with hyperprolactinemia in old female rats because they are known to release prolactin through hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons. Hypothalamic kisspeptin neurons are thus the main regulator to secrete LH, and inhibition of kisspeptin expression leads to various kinds of reproductive dysfunction.","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"52 1","pages":"85 - 91"},"PeriodicalIF":2.4,"publicationDate":"2019-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1267/ahc.19013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42066040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reversible Conversion among Subtypes of Salivary Gland Duct Cells as Identified by Production of a Variety of Bioactive Polypeptides","authors":"S. Kurabuchi, C. Yao, Gang Chen, K. Hosoi","doi":"10.1267/ahc.19014","DOIUrl":"https://doi.org/10.1267/ahc.19014","url":null,"abstract":"Four major kallikreins (mK1, mK22, mK9, and mK13) were identified in the mouse submandibular gland (SMG). mK1, a true tissue kallikrein, was used as a protein marker to identify different types of SMG granular convoluted tubule (GCT) cells along with epidermal growth factor (EGF), nerve growth factor (NGF), and renin. Kallikrein mK1 was localized in a very small number (~5%) of GCT cells, which were scattered throughout the GCT, indicating that the majority of GCT cells are mK1-negative. Among mK1-positive cells, particularly strong signals were observed in a small number of narrow cells, recognized as slender granular cells (SG cells, Type IV), in the GCT. After postnatal development of the SMG, GCT cells are no longer uniform based on the bioactive substances (mK1, EGF, NGF, and renin) that they produce and secrete. GCT cells were classified into four subtypes, Types I–IV, and it became clear that these subtypes are complicatedly and reversibly converted by the endocrine hormones 5α-dihydrotestosterone (DHT) and triiodothyronine (T3). Duct segments with similar morphology or hormone dependency were recognized in the sublingual and parotid glands. The presence of duct cells with such characteristics is therefore a common feature of the three major salivary glands of rodents.","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"52 1","pages":"59 - 65"},"PeriodicalIF":2.4,"publicationDate":"2019-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1267/ahc.19014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42656424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Naparee Srisowanna, N. Choijookhuu, Koichi Yano, Baatarsuren Batmunkh, Makoto Ikenoue, Nguyen Nhat Huynh Mai, Y. Yamaguchi, Y. Hishikawa
{"title":"The Effect of Estrogen on Hepatic Fat Accumulation during Early Phase of Liver Regeneration after Partial Hepatectomy in Rats","authors":"Naparee Srisowanna, N. Choijookhuu, Koichi Yano, Baatarsuren Batmunkh, Makoto Ikenoue, Nguyen Nhat Huynh Mai, Y. Yamaguchi, Y. Hishikawa","doi":"10.1267/ahc.19018","DOIUrl":"https://doi.org/10.1267/ahc.19018","url":null,"abstract":"Fatty liver is common in men and post-menopausal women, suggesting that estrogen may be involved in liver lipid metabolism. The aim of this study is to be clear the role of estrogen and estrogen receptor alpha (ERα) in fat accumulation during liver regeneration using the 70% partial hepatectomy (PHX) model in male, female, ovariectomized (OVX) and E2-treated OVX (OVX-E2) rats. Liver tissues were sampled at 0–48 hr after PHX and fat accumulation, fatty acid translocase (FAT/CD36), sterol regulatory element-binding protein (SREBP1c), peroxisome proliferator-activated receptor α (PPARα), proliferative cell nuclear antigen (PCNA) and ERα were examined by Oil Red O, qRT-PCR and immunohistochemistry, respectively. Hepatic fat accumulation was abundant in female and OVX-E2 compared to male and OVX rats. FAT/CD36 expression was observed in female, OVX and OVX-E2 at 0–12 hr after PHX, but not in male rats. At 0 hr, SREBP1c and PPARα were elevated in female and male rats, respectively, but were decreased after PHX in all rats. The PCNA labeling index reached a maximum at 36 hr and 48 hr in OVX-E2 and OVX rats, respectively. ERα expression in OVX-E2 was higher than OVX at 0–36 hr after PHX. In conclusion, these results indicated that estrogen and ERα might play an important role in fat accumulation related to FAT/CD36 during early phase of rat liver regeneration.","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"52 1","pages":"67 - 75"},"PeriodicalIF":2.4,"publicationDate":"2019-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1267/ahc.19018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42672386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Kitazawa, Ryuma Haraguchi, Y. Kohara, R. Kitazawa
{"title":"Modulation of αvβ3 Integrin via Transactivation of β3 Integrin Gene on Murine Bone Marrow Macrophages by 1,25(OH)2D3, Retinoic Acid and Interleukin-4","authors":"S. Kitazawa, Ryuma Haraguchi, Y. Kohara, R. Kitazawa","doi":"10.1267/ahc.19015","DOIUrl":"https://doi.org/10.1267/ahc.19015","url":null,"abstract":"The interleukin (IL)-4, 1,25(OH)2D3 and retinoic acid, increase surface expression of functional integrin αvβ3 on murine osteoclast precursors. All three agonists stimulate transcription of the β3 gene, leading to increased steady-state levels of mRNA this protein. By contrast, mRNA levels of αv remain unchanged. In each instance, the increase in the surface expression of the integrin results in increased migration of the cells onto an αvβ3 substrate. Because β3 subunit, except platelet where β3 subunit conform a dimer with αIIb, associates solely with αv subunit monogamously, while promiscuous αv subunit combines with various subunit, our present data support the idea that the β3 subunit governs the surface-expressed functional integrin complex.","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"93 1","pages":"77 - 83"},"PeriodicalIF":2.4,"publicationDate":"2019-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1267/ahc.19015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41276336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Akie Taniguchi, T. Susa, H. Kogo, A. Iizuka-Kogo, S. Yokoo, T. Matsuzaki
{"title":"Long-term Pilocarpine Treatment Improves Salivary Flow in Irradiated Mice","authors":"Akie Taniguchi, T. Susa, H. Kogo, A. Iizuka-Kogo, S. Yokoo, T. Matsuzaki","doi":"10.1267/ahc.19006","DOIUrl":"https://doi.org/10.1267/ahc.19006","url":null,"abstract":"Radiation therapy for head and neck cancer frequently causes salivary gland dysfunction. Pilocarpine is a clinically approved and effective drug that induces saliva secretion, thereby keeping the oral mucosa moist and reducing discomfort in patients, but the effect is transient. We expected that this drug also has beneficial long-term effects that maintain the integrity of salivary glands by reducing, for instance, apoptosis. Here, we examined the effects of long-term pilocarpine administration in irradiated mice. The results indicated that long-term pilocarpine administration significantly improved salivary flow in irradiated mice, suggesting the potential beneficial effects of long-term administration. To elucidate the underlying mechanism, we analyzed the histology, apoptosis, and proliferation of acinar cells, and the expression of functional membrane proteins such as transmembrane member 16A, aquaporin-5, and Na-K-Cl cotransporter. Long-term pilocarpine treatment seemed to decrease irradiation-induced apoptosis, although the change was not statistically significant. The present results indicated that long-term administration of pilocarpine has beneficial effects on salivary flow in irradiated mice, and suggested that long-term administration possibly decreases apoptosis in irradiated salivary glands.","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"52 1","pages":"45 - 58"},"PeriodicalIF":2.4,"publicationDate":"2019-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1267/ahc.19006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46858821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of the Wnt Signaling Pathway in Upper Jaw Development of Chick Embryo.","authors":"Tadahiro Shimomura, Masayoshi Kawakami, Kouko Tatsumi, Tatsuhide Tanaka, Shoko Morita-Takemura, Tadaaki Kirita, Akio Wanaka","doi":"10.1267/ahc.18038","DOIUrl":"https://doi.org/10.1267/ahc.18038","url":null,"abstract":"<p><p>Cleft lip with or without cleft palate (CLP) usually results from a failure of the medial nasal prominences to fuse with the lateral and maxillary prominences. This failure inhibits facial morphogenesis regulated by several major morphogenetic signaling pathways. We hypothesized that CLP results from the failure of the Wnt signaling pathway. To examine whether Wnt signaling can influences upper jaw development, we applied beads soaked with Dickkopf-1 (Dkk-1), Alsterpaullone (AL) or Wnt3a to the right side of the maxillary prominence of the chick embryo. The embryo showed a defect of the maxilla on the treated side, and skeletal staining revealed hypoplasia of the premaxilla and palatine bone as a result of Dkk-1-soaked bead implantation. 5-bromo-2'-deoxyuridine (BrdU)-positive cell numbers in the treated maxillary prominence were significantly lower at both 24 and 48 hr after implantation. Down-regulation of the expression of <i>Bmp4</i>, <i>Tbx22</i>, <i>Sox9</i>, and <i>Barx1</i> was confirmed in the maxillary prominence treated with Dkk-1, which indicated that the deformity of the maxillary bone was controlled by gene targets of the Wnt signaling pathway. Expression of N-cadherin was seen immunohistochemically in the maxillary prominences of embryos at 6 hr and increased at 24 hr after AL treatment. Wnt signaling enhanced by AL or Wnt3a up-regulated the expression levels of <i>Msx1</i>, <i>Bmp4</i>, <i>Tbx22</i>, <i>Sox9</i>, and <i>Barx1</i>. Our data suggest that the Wnt signaling pathway regulates maxillary morphogenesis and growth through <i>Bmp4</i>, <i>Tbx22</i>, <i>Sox9</i>, and <i>Barx1</i>. Wnt signaling might regulate N-cadherin expression via <i>Msx1</i>, resulting in cell aggregation for osteochondrogenesis.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"52 1","pages":"19-26"},"PeriodicalIF":2.4,"publicationDate":"2019-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1267/ahc.18038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37101493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}