Histology and histopathology Vol.34, nº7 (2019)
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- PublicationOpen AccessReduction of PGRN increased fibrosis during skin wound healing in mice(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Li, Shan-shan; Zhang, Mei Xiang; Wang, Yue; Wang, Wei; Zhao, Chun Ming; Sun, Xiao Ming; Dong, Guo Kai; Li, Zhou Ru; Yin, Wen Jiang; Zhu, Bo; Cai, Hong XingProgranulin (PGRN) is a multi-functional growth factor known to be involved in regulating of development, cell cycle progression, cell motility, tumorigenesis and angiogenesis. Research has revealed that PGRN is a crucial mediator of skin wound healing. Nonetheless, the role of PGRN in the fibrosis process of cutaneous wound healing has not been identified. In the present study, mice with excisional wounds were treated with si-m-PGRN or physiological saline. We observed the expression of PGRN in intact and post-injury skin by immunohistochemistry. Tissue sections of skin around the wound were performed by hematoxylin and eosin and masson's trichrome staining. After PGRN knockdown by siRNA, the expression of PGRN, collagen I (Col I), small mothers against decapentaplegic homolog 3 (Smad3), phosphorylated Smad3 (P-Smad3), transforming growth factor (TGF)-β1 and TGF-β receptor I (TβRI) were detected by real-time reverse transcription polymerase chain reaction (RT-qPCR) or Western blot. PGRN mRNA and protein expressions were increased after insult and remained above that of intact skin through day 20. Down-regulation of PGRN augmented fibrosis area, skin thickness and the expression of Col I. In addition, reduction of PGRN considerably increased the expression of TGF-β1, TβRI, Smad3 and P-Smad3. These results indicate that PGRN knockdown enhances the fibrosis degree, probably via the TGF-β/Smad signaling pathway.
- PublicationOpen AccessMorphological rearrangement of the cortical region, in aging ovaries(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Díaz Hernández, Verónica; Caldelas, Ivette; Montaño, Luis M.; Merchant Larios, HoracioThe ovary is a structurally dynamic organ that alters with age. Modifications in the paracrine status influence the capacity of aging oocytes to develop normal embryos. Despite the importance of understanding the cellular and molecular mechanism involved in the process of ovarian aging, histological changes remain poorly understood. Correlating the process of folliculogenesis and somatic cell function during ovarian aging is essential to explain the reproductive decline of aged mammalian species, including humans. Here, we performed a morphological and immunohistological study on the ovaries of chinchilla rabbits that varied in age from one to 34-months. The spatiotemporal expression of the cholesterol side-chain cleavage cytochrome P450scc (CYP11A) and the smooth muscle actin (SMA) were analyzed. A significant histological rearrangement of immunodetected cells in theca interna, theca externa and the interstitial tissue around the follicles occurred. The expression of CYP11A1 decreased considerably in antral follicles of aging ovaries. Moreover, we found that the secondary interstitial gland developed extensively, and a remarkable rearrangement of the surface epithelium occurred in aging ovaries. In contrast to ovaries during the reproductive period, the immunohistological changes demonstrate that the interstitial gland became the most abundant tissue during the aging of ovaries. Thus, the current study provides new data for understanding the alteration of somatic cell function in elderly ovaries and how this affects their declined fertility.
- PublicationOpen AccessCharacterization of the early pathology of cochlear stereocilia in four inbred mouse strains with progressive hearing loss(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Liu, Xiang; Xie, Yi; Huang, Shanshan; Xu, Ang; Zhao, Mengmeng; Kang, Xiaoxia; Yan, Aiwei; Li, Ping; Jin, Changzhu; Han, FengchanObjective. Inbred strains of mice offer promising models for understanding the genetic basis of age-related hearing loss (AHL). NOD/LtJ, A/J, DBA/2J and C57BL/6J mice are classical models of age-related hearing loss and exhibit early onset of pathology of AHL. This study was carried out to characterize the early pathology of cochlear stereocilia in the four mouse strains with age-related hearing loss. Methods. The structural features of stereocilia in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice were observed by scanning electron microscopy (SEM) at age of 2, 4, 6 or 8, and 10 or 12 weeks. Meanwhile, auditoryevoked brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) amplitudes of the mice were measured at various intervals (3, 4, 6, 8, 10 and 12 weeks of age). Results. The ABR thresholds in NOD/LtJ, A/J and DBA/2J mice increased with age from 3 to 12 weeks. DPOAE amplitudes in NOD/LtJ, A/J, DBA/2J mice were very low at 4 weeks and became negative at 8 weeks at f2 frequency of 17 672 Hz. In addition to the progressive hearing loss, the four mouse strains displayed early onset (at 2 weeks of age) and progressive degeneration of stereocilia in hair cells. Conclusion. Early degeneration of stereocilia contributes to the functional impairment of hair cells and hearing loss in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice.
- PublicationOpen AccessSafety of isotretinoin treatment as measured by liver parameters(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Thomazini, B.F.; Lamas, C.A.; Dolder, M.A.H.Isotretinoin is an analogue of vitamin A and by suppressing the sebaceous glands it is often prescribed in cases of severe acne treatment. The treatment for the average patient is carried out during two to ten months. This study was designed to investigate liver structure, hepatic enzyme levels and the stress oxidative parameter after isotretinoin treatment during a similar period and using the dosages of 1 mg/kg and another one of 10 mg/kg in young male Wistar rats. We have analyzed the blood serum biochemical levels to determine hepatic function and lipid peroxidation, hepatic tissue levels of hepatic enzymes, histology and ultrastructure. The groups receiving 1 mg/kg were not altered after treatment. Their ultrastructure showed a metabolically more active organ after treatment with 10 mg/kg, in which there was an increase in the area occupied by mitochondria and rough reticulum in electron transmission images. The group that received 10 mg/kg also showed increased alkaline phosphatase, decreased high density lipoprotein and low density lipoprotein. The changes observed with the 10 mg/kg dose were not conclusive for liver damage, because of the lack of histological structural modifications and the few biochemical alterations. The 1 mg/kg dose showed a liver responding to some stimuli but without profound alterations. So, we confirm that the proposed protocol with 1 mg/kg or 10 mg/kg isotretinoin did not cause important biochemical and histological disfunctions for male Wistar rat livers.
- PublicationOpen AccessSynergism of imatinib, vatalanib and everolimus in the prevention of chronic lung allograft rejection after lung transplantation (LTx) in rats(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Keil, Laura; Schaub, Anna Lena; Hirt, Stephan W.; Schmid, Christof; Lehle, Karla; Suesskind Schwendi, Marietta vonChronic lung allograft dysfunction (CLAD) still remains a major drawback in the outcome following lung transplantation (LTx). New therapeutic strategies are warranted. Growth factors and their receptors like platelet-derived growth factor-receptor (PDGFR) and vascular endothelial growth factor-receptor (VEGFR), may play a crucial role in the development of CLAD, especially bronchiolitis obliterans (BO) and vasculopathy. In this study, we used an orthotopic left lung transplantation model from Fischer (F344) to Wystar Kyoto (WKY) rats to investigate the effect of the receptor tyrosine kinase inhibitor (RTKI) vatalanib alone, the dual combination of the RTKIs vatalanib and imatinib and a triple therapy consisting of vatalanib, imatinib and the mammalian target of rapamycin inhibitor (mTORI) everolimus on the development of CLAD after LTx in rats. With this trial we demonstrated that monotherapy with vatalanib attenuated mild and severe chronic vascular rejection, whereas dual therapy (vatalanib and imatinib) after LTx also showed a significant reduction of chronic bronchiolar rejection and interstitial fibrosis. By adding everolimus, the effect of vatalanib and imatinib could additionally be increased. In conclusion, the combination of mTORI and RTKIs might be a possible strategy in the prevention of CLAD and BO.
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