25 research outputs found
Pathology of primary open angle glaucoma (POAG)
No full textPh.D.Glaucoma, a leading cause of irreversible blindness worldwide, is a heterogeneous group of optic neuropathies characterized by cupping of the optic nerve head and visual field damage. Primary open angle glaucoma (POAG) is the most common type of glaucoma. According to the highest intra ocular pressure (IOP), POAG have been conventionally divided into high tension POAG (HTG, IOP > 21 mmHg) and normal tension POAG (NTG, IOP ≤ 21 mmHg).IOP is a major risk factor for POAG and lowering IOP is currently the only intervention that has been proven to be able to delay the progression of the disease. Trabecular meshwork / Schlemm’s canal (TM / SC) conventional aqueous humor (AH) outflow pathway plays a key role in the regulation of IOP. These trabecular meshwork cells in the TM / SC outflow pathway are constantly subjected to oxidative stress attack generated from the physiological cellular metabolism. Oxidative stress represents increased intracellular reactive oxygen species (ROS) levels that could damage DNA, proteins and lipids. The lack of effective antioxidant mechanism in the TM may lead to cell decay, causing both morphological and functional alterations of the TM tissues. This scenario subsequently results in an increased AH outflow resistance and eventually IOP elevation. Autophagy is an essential and adaptive cellular survival mechanism to protect cells against various cellular stresses, including oxidative damages. These observations led to a hypothesis that inducing autophagy biochemically may relieve chronic oxidative stress in TM, and therefore alleviate the IOP elevation and the risk of having glaucoma. Currently IOP lowering agents mainly involve reducing the production of AH or promoting AH outflow through the unconventional intercellular space between ciliary muscle cells. These agents can only resolve the high IOP temporarily. On the other hand, as the TM / SC conventional AH outflow pathway controls more than 75% of the AH outflow, the knowledge about the autophagy in response to chronic oxidative stress in TM cells may help develop new therapeutic strategies to POAG. In this thesis, I aim to study the roles of autophagy in POAG. In the first part, I evaluated the roles of rapamycin in protecting TM cells from oxidative stress. In the second part, I screened for coding sequence variations in OPTN, an important gene in regulating autophagy, in Chinese NTG patients. In the third part, I further characterized the H486R OPTN mutation in TM cells.In this first part of this thesis, I induced chronic oxidative stress in human trabecular meshwork (TM 1) cells with 1 μM rotenone and investigated the levels of reactive oxygen species (ROS), autophagy and mitochondrial functions. Protective effects of rapamycin, an inducer of autophagy, were also investigated. Our data indicated that rotenone significantly increased oxidative stress, but not autophagy, in TM 1 cells. Rapamycin at 10 nM effectively suppressed the rotenone induced cell apoptosis, as well as the ROS elevation. The protective effects of rapamycin could be associated to the induction of autophagy and removal of damaged mitochondria in TM 1 cells. Our results suggest autophagy has important roles in protecting TM 1 cells from oxidative stress, which could be further developed into a novel treatment to POAG.Optineurin (OPTN) is a receptor of autophagy. In the eye, optineurin is expressed in the TM, nonpigmented ciliary epithelium, and remarkably in the retina. The optineurin protein contains an ubiquitin binding domain (UBD) (445 502 aa) and a LC3 interacting region (LIR) (169 184 aa), which allows optineurin to act like a bridge to bring ubiquitinated cargos to the autophagosome via LC3. In 2002, FIP 2 mutations were identified responsible for POAG in 54 families and this gene was renamed as “optineurin” (OPTN). Most of these families showed normal levels of IOP. Since then plenty of OPTN alternations were found in glaucoma patients. The subsequent studies did not show a statistical significant correlation of OPTN exclusively with HTG and there were variations in the frequency of coding and noncoding polymorphisms within OPTN in NTG among different ethnicity. So in the second of this thesis, I did OPTN coding region mutation screening in NTG among Chinese patients.Genomic DNA was extracted from 190 NTG patients and 201 control subjects. The thirteen (exon 4 16) exons of OPTN were amplified by polymerase chain reaction and analyzed by direct sequencing. Detected sequence changes were compared between NTG patients and control subjects. Seven sequence changes in OPTN were identified in both NTG patients and control subjects. Among them, c. 464G>A (T34T), c. 509C>T (T49T), c. 806G>A (V148V) and c. 959T>C (P199P) were synonymous codon changes, whilst c. 655T>A (M98K), c. 1996G>A (R545Q) and c. 1582T>C (I407T) were missense changes. Two previously reported heterozygous mutations, c.458G>A (E50K) in exon 4 and c.691_692insAG in exon 6, were not found in this study. Out of these seven OPTN sequence variants, c. 464G>A (T34T) was significantly associated with NTG in both the allelic and genotypic association analyses (allelic association: p = 0.0001, OR=2.20, 95% CI 1.46 3.31; genotypic association: p = 0.0001), whereas the association of other variants with NTG did not reach statistical significance (p>0.05). Variants c. 1582T>C (I407T) and c. 806G>A (V148V) were identified in one and two NTG patients, respectively, but not in control subjects.To further study the biological roles of these OPTN mutations, six sites on OPTN were mutated (E50K, M98K, S177A, S473A, H486R and S513A) to investigate their consequences in TM 1 cells under induced oxidative stress. Although some of these mutations were not found in our genetics study, they were still included for the functional investigations because of their important reported roles in autophagy and POAG. E50K, M98K and H486R were identified in POAG patients. S177A, S473A and S513A were loss of function mutations at the Tank binding kinase 1 (TBK1) phosphorylation sites, which have been reported to cause defective autophagy. M98K was the missense codon change identified in this study. E50K showed a strong association with POAG, particularly with NTG. M98K and E50K are located in the TBK1 binding domain of OPTN (1 127 aa). H486R, located in the UBD of optineurin, was identified in POAG patient but not in control subjects. The oxidative stress levels, numbers of damaged mitochondria and apoptosis levels in the wild type (WT) and mutant OPTN expressing TM 1 cells were investigated. Our results showed that H486R OPTN expressing cells had higher endogenous and induced oxidative stress levels than the WT OPTN expressing cells. More damaged mitochondria and higher apoptosis levels were also detected in H486R OPTN expressing cells. These results indicated H486R mutation in OPTN would affect the cellular functions of TM 1 cells. Further studies are needed to confirm the impacts of H486R OPTN in autophagy as this mutation site is situated in the UBD region, which is predicted to deliver the ubiquitinated cargos to the autophagosome. Our study could provide a preliminary understanding of the roles of OPTN H486R in regulating autophagy in TM cells, which suggest a role for the H486R OPTN mutation in POAG. These results could serve as a proof of concept to support the feasibility of this experimental approach in characterizing OPTN mutations. The same experimental approach could be used to study the other five variants.In conclusion, the defective optineurin function caused by H486R mutation would affect the cellular function of TM cells which may contribute to some of the pathologies of POAG. Also, the induction of autophagy level could protect TM cells from oxidative stress. Further exploring in the roles of autophagy may help develop new therapeutic strategies to POAG.青光眼是世界範圍內導致不可逆性失明的主要原因，是一組異質性視神經病變，其特征是視神經乳頭杯狀凹陷和視野損害。原發性開角型青光眼(POAG)是最常見的青光眼類型。根據最高眼壓(IOP)，POAG通常被分為高壓性POAG (HTG，眼壓>21 mmHg)和正常眼壓性POAG (NTG，眼壓≤21 mmHg)。眼壓是POAG的主要危險因素，降低眼壓是目前唯一被證明能夠延緩疾病進展的干預措施。小梁網/Schlemm管(TM/SC)的傳統房水流出通路在調節眼壓中起著關鍵作用。TM/SC流出途徑中的這些小梁網絡細胞不斷受到細胞生理代謝產生的氧化應激的攻擊。氧化應激表現為細胞內活性氧(ROS)水平增加，可破壞DNA、蛋白質和脂質。小梁網中缺乏有效的抗氧化機制可能導致細胞衰變，導致小梁網組織的形態和功能改變。這種情況隨後導致房水流出阻力增加，並最終導致眼壓升高。自噬是一種必要的適應性細胞生存機制，可以保護細胞免受各種細胞應激，包括氧化損傷。這些觀察結果導致了一個假設，即通過生物化學誘導自噬可以緩解TM中的慢性氧化應激，從而減輕眼壓升高和患青光眼的風險。目前眼壓降低劑主要涉及減少房水的產生或通過睫狀肌細胞間的非常規細胞間隙促進房水流出。這些藥劑只能暫時解決高眼壓問題。另一方面，由於TM/SC傳統的房水流出途徑控制著超過75%的房水流出，了解小梁網細胞對慢性氧化應激反應的自噬可能有助於開發新的POAG治療策略。本論文目標是研究自噬在POAG的角色。第一部分研究雷帕黴素在保護人小梁網細胞免受氧化應激的角色。第二部分研究自噬受體OPTN在中國NTG患者中的外顯子序列變化。第三部分探討H486R OPTN突變對人小梁網細胞的影響。在這項研究中，我們用1 µM魚藤酮誘導了人小梁網(TM-1)細胞的慢性氧化應激，並研究了活性氧(ROS)、自噬和線粒體功能的水平。同時還研究了自噬誘導劑雷帕黴素的保護作用。我們的數據表明魚藤酮顯著增加了TM-1細胞的氧化應激，但沒有增加自噬。雷帕黴素在10 nm有效地抑制魚藤酮誘導的細胞凋亡，以及ROS的升高。雷帕黴素的保護作用可能與誘導TM-1細胞自噬和清除受損線粒體有關。我們的結果表明自噬在保護TM-1細胞免受氧化應激中具有重要作用，這可以進一步發展為種治療POAG的新方法。Optineurin(OPTN)是自噬的受體。在眼睛中，optineurin在小梁網，無色素睫狀體上皮，特別是視網膜中表達。Optineurin蛋白包含泛素結合結構域(UBD)(445-502 aa)和LC3相互作用區域(LIR)(169-184 aa)，這就使得optineurin能夠充當橋梁，通過LC3將泛素化的貨物帶到自噬體內。2002年，在54個家庭中發現了導致POAG的FIP-2突變，並將該基因重命名為“optineurin”(OPTN)。這些家庭中的大多數顯示出正常的眼壓水平。從那時起，在青光眼患者中發現了大量的OPTN改變。隨後的研究沒有顯示OPTN與HTG獨有的統計顯著相關性，並且在不同種族中，NTG中OPTN內編碼和非編碼多態性的頻率存在差異。因此，我們在中國患者中進行了NTG中OPTN編碼區突變篩查。提取190例NTG患者和201例對照組的基因組DNA。用聚合酶鏈反應擴增OPTN的13個外顯子(第4-16外顯子)，直接測序分析。將檢測到的序列變化在NTG患者和對照組之間進行比較。在NTG患者和對照組中都發現了OPTN的7個序列變化。其中c.464G>A(T34T)，c.509C>T(T49T)，c.806G>A(V148V)和c.959T>C(P199P)為同義密碼子變化，c.655T>A(M98K)，c.1996G>A(R545Q)和c.1582T>C(I407T)為錯義突變。本研究未發現先前報道的兩個雜合突變，即外顯子4中的C.458G>A(E50K)和外顯子6中的C.691_692insAG。在這7個OPTN序列變異中，c.464G>A(T34T)在等位基因和基因型關聯分析中均與NTG顯著相關(等位基因關聯：P=0.0001，OR=2.2 0，95%置信區間1.46-3.31；基因型關聯：P=0.0001)，而其他變異與NTG的關聯無統計學意義(p>0.05)。分別在1例和2例NTG患者中發現c.1582T>C(I407T)和c.806G>A(V148V)變異，但在對照組中未發現。為了進一步研究這些OPTN突變的生物學作用，我們對OPTN上的6個位點(E50K，M98K，S177A，S473A，H486R和S513A)進行了突變，以研究它們在誘導氧化應激下在TM-1細胞中的影響。雖然有一些突變沒有在我們的研究中發現，但它們仍然被包括在內，因為它們在自噬和POAG中的有著重要角色。E50K、M98K和H486R是在POAG患者中發現的。S177A，S473A和S513A是Tank結合激酶1(TBK1)磷酸化位點的功能喪失突變，已有報道它們可導致缺陷自噬。M98K是本研究中發現的錯義密碼子改變。E50K與POAG，特別是NTG有很強的相關性。M98K和E50K位於OPTN(1-127aa)的TBK1結合結構域。在POAG患者中發現了位於optineurin泛素結合結構域中的H486R，而在對照組中未發現H486R。我們研究了表達TM-1的野生型(WT)和突變體OPTN細胞的氧化應激水平、線粒體損傷數量和凋亡水平。我們的結果表明，表達H486R OPTN的細胞比表達WT OPTN的細胞具有更高的內源性和誘導氧化應激水平。在表達H486R OPTN的細胞中也檢測到更多的線粒體損傷和更高的凋亡水平。這些結果表明OPTN中的H486R突變會影響TM-1細胞的細胞功能。這還需要進一步的研究來證實H486R OPTN在自噬中的影響，因為這個突變位點位於泛素結合結構域，預測泛素結合結構域將泛素化的貨物運送到自噬體內。我們的研究可以初步了解OPTN H486R在調節TM細胞自噬中的作用，並為建立POAG中H486R OPTN突變的作用提供機制基礎。同樣的實驗方法也可以用來研究其他五個變異體。總之，H486R突變引起的Optineurin功能缺陷會影響TM細胞的細胞功能，這可能與POAG的某些病理過程有關。此外，誘導自噬水平可以保護TM細胞免受氧化應激的影響。進一步探討自噬的作用可能有助於開發新的POAG治療策略。He, Jingna.Thesis Ph.D. Chinese University of Hong Kong 2019.Includes bibliographical references (leaves 134-174).Abstracts also in Chinese.Title from PDF title page (viewed on 14 May, 2021)
A comparison of clinical outcomes between endoscopic and open surgery to repair neonatal diaphragmatic hernia
No full textObjective: The objective of this study is to evaluate the clinical efficacies of open versus endoscopic surgery in the treatment of congenital diaphragmatic hernia (CDH) and investigate the feasibility and safety of endoscopic surgery as an alternative to open surgery in these cases. Patients and Methods: A retrospective analysis was performed from June 2002 to February 2014. A total of 59 cases were attempted. The neonates were divided into either an endoscopic or open surgery group. The pre-, intra- and post-operative data on the neonates were analysed, and the surgery-related complications, survival rates and recurrence rates were compared between the two groups. Results: Demographic characteristics were not significantly different between the two groups. Compared with open group, the hospital stay and post-operative mechanical ventilation time were significantly shorter, while surgery duration was significantly longer in the endoscopic surgery group. The recurrence rate was higher and the survival rate was lower in the endoscopic surgery group with no statistically significant and the recurrence rate has decreased over the past 5 years. Conclusions: We have demonstrated that the endoscopic surgery is safe and effective for repairing CDH. The endoscopic surgery is a minimally invasive procedure with fast post-operative recovery and a good cosmetic outcome
Optimal Scheduling Model of WDM/OTN Network Transmission Line Based on Machine Learning
No full textIn order to solve the problem that the influencing factors are difficult to parameterize in the design and development of WDM/OTN backbone network routing planning tools, the author proposes an optimal scheduling model for WDM/OTN network transmission lines based on machine learning. Using the machine learning classification algorithm as a tool, the weight coefficients of each constraint factor are extracted from the historical design decisions, and the routing parameter model is constructed, so as to realize the intelligent routing selection, through actual simulation analysis and engineering verification. Simulation results show that after the historical routing regression test, the path coincidence rate of the route obtained by the algorithm and the historical real decision-making route reaches 81%, and the resource hit rate reaches 84%, which meets the requirements for actual production. Conclusion. This method can accurately and effectively generate network weight parameters so that the software routing is more intelligent
Mining On Alzheimer's Diseases Related Knowledge Graph to Identity Potential AD-related Semantic Triples for Drug Repurposing
No full textTo date, there are no effective treatments for most neurodegenerative
diseases. Knowledge graphs can provide comprehensive and semantic
representation for heterogeneous data, and have been successfully leveraged in
many biomedical applications including drug repurposing. Our objective is to
construct a knowledge graph from literature to study relations between
Alzheimer's disease (AD) and chemicals, drugs and dietary supplements in order
to identify opportunities to prevent or delay neurodegenerative progression. We
collected biomedical annotations and extracted their relations using SemRep via
SemMedDB. We used both a BERT-based classifier and rule-based methods during
data preprocessing to exclude noise while preserving most AD-related semantic
triples. The 1,672,110 filtered triples were used to train with knowledge graph
completion algorithms (i.e., TransE, DistMult, and ComplEx) to predict
candidates that might be helpful for AD treatment or prevention. Among three
knowledge graph completion models, TransE outperformed the other two (MR =
13.45, Hits@1 = 0.306). We leveraged the time-slicing technique to further
evaluate the prediction results. We found supporting evidence for most highly
ranked candidates predicted by our model which indicates that our approach can
inform reliable new knowledge. This paper shows that our graph mining model can
predict reliable new relationships between AD and other entities (i.e., dietary
supplements, chemicals, and drugs). The knowledge graph constructed can
facilitate data-driven knowledge discoveries and the generation of novel
hypotheses.Comment: BMC Bioinformatic
Recommended from our members
Antitumor activity of curcumin is involved in down-regulation of YAP/TAZ expression in pancreatic cancer cells
No full textPancreatic cancer (PC) is one of the most aggressive human malignancies worldwide and is the fourth leading cause of cancer-related deaths. Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Certain studies have demonstrated that curcumin exerts its anti-tumor function in a variety of human cancers including PC, via targeting multiple therapeutically important cancer signaling pathways. However, the detailed molecular mechanisms are not fully understood. Two transcriptional co-activators, YAP (Yes-associated protein) and its close paralog TAZ (transcriptional coactivator with PDZ-binding motif) exert oncogenic activities in various cancers. Therefore, in this study we aimed to determine the molecular basis of curcumin-induced cell proliferation inhibition in PC cells. First, we detected the anti-tumor effects of curcumin on PC cell lines using CTG assay, Flow cytometry, clonogenic assay, wound healing assay and Transwell invasion assay. We found that curcumin significantly suppressed cell growth, weakened clonogenic potential, inhibited migration and invasion, and induced apoptosis and cell cycle arrest in PC cells. We further measured that overexpression of YAP enhanced cell proliferation and abrogated the cytotoxic effects of curcumin on PC cells. Moreover, we found that curcumin markedly down-regulated YAP and TAZ expression and subsequently suppressed Notch-1 expression. Collectively, these findings suggest that pharmacological inhibition of YAP and TAZ activity may be a promising anticancer strategy for the treatment of PC patients.Version of Recor
Research hotspots and trends in nursing for diabetic foot ulcers: A bibliometric analysis from 2013 to 2023
No full textBackground: Nursing can effectively prevent and ameliorate diabetic foot ulcers (DFU). However, there is a lack of literature on the bibliometric analysis of DFU nursing. This study aimed to analyze the research hotspots and development trends in DFU nursing over the past 10 years to provide references for future related research. Methods: The Web of Science Core Collection was used to retrieve literature related to DFU nursing from 2013 to 2023. Analyses included the annual publication trends; author, institution, and country collaborations; journal and literature co-citation; and keyword co-occurrence, clustering, and bursting, performed using CiteSpace 5.8 R3. Results: A total of 229 papers were included, showing an upward trend in annual publications. American scholar David G Armstrong (n = 3) and King's College Hospital London (n = 4) were the most productive authors and institutions, respectively. The United States ranked first (n = 45) in national contributions, followed by China and Brazil. The overall research strength between authors and institutions was relatively scattered, and intensive cooperation has not yet been formed. National collaborations resulted in a core team dominated by Europe and North America with concentrated research strengths. The most frequently co-cited journal and co-cited reference were Diabetes Care (111 citations) and Armstrong DG (2017) (131 citations), separately. Research hotspots mainly focused on risk assessment, classification systems, protective measures, and clinical management of DFU. “Primary care” and “intervention efficacy” were identified as the research trends in the coming years. Conclusion: The field of DFU nursing requires more attention. Academic exchange and cooperation between authors, institutions, and countries should be strengthened. Our future research will focus on the latest hotspots and trends, conducting more in-depth and comprehensive studies on DFU management
Inhibition of Notch-1 pathway is involved in rottlerin-induced tumor suppressive function in nasopharyngeal carcinoma cells
No full textRecent studies have revealed that rottlerin is a natural chemical drug to exert its anti-cancer activity. However, the molecular mechanisms of rottlerin-induced tumor suppressive function have not been fully elucidated. Notch signaling pathway has been characterized to play a crucial role in tumorigenesis. Therefore, regulation of Notch pathway could be beneficial for the treatment of human cancer. The aims of our current study were to explore whether rottlerin could suppress Notch-1 expression, which leads to inhibition of cell proliferation, migration and invasion in nasopharyngeal carcinoma cells. We performed several approaches, such as CTG, Flow cytometry, scratch healing assay, transwell and Western blotting. Our results showed that rottlerin treatment inhibited cell growth, migration and invasion, and triggered apoptosis, and arrested cell cycle to G1 phase. Moreover, the expression of Notch-1 was obvious decreased in nasopharyngeal carcinoma cells after rottlerin treatment. Importantly, overexpression of Notch-1 promoted cell growth and invasion, whereas down-regulation of Notch-1 inhibited cell growth and invasion in nasopharyngeal carcinoma cells. Notably, we found the over-expression of Notch-1 could abrogate the anti-cancer function induced by rottlerin. Strikingly, our study implied that Notch-1 could be a useful target of rottlerin for the prevention and treatment of human nasopharyngeal carcinoma.Version of Recor
Association between risk of Alzheimer’s disease and related dementias and angiotensin receptor Ⅱ blockers treatment for individuals with hypertension in high-volume claims dataResearch in context
No full textSummary: Background: Findings regarding the protective effect of Angiotensin II receptor blockers (ARBs) against Alzheimer’s disease and related dementias (AD/ADRD) and cognitive decline have been inconclusive. Methods: Individuals with hypertension who do not have any prior ADRD diagnosis were included in this retrospective cohort study from Optum’s de-identified Clinformatics® Data Mart. We identified antihypertensive medication (AHM) drug classes and subclassified ARBs by blood–brain barrier (BBB) permeability. We compared baseline characteristics and used the Kaplan–Meier (KM) survival curve and adjusted Cox proportional hazards (PH) model for survival analyses. Findings: From 6,390,826 individuals with hypertension, there were 1,839,176 ARB users, 3,366,841 non-ARB AHM users, and 1,184,809 AHM non-users. The unadjusted KM curve showed that ARB users had lower cumulative hazard than other AHM users or AHM non-users (P < 0.0001). In Cox PH analysis, ARB users showed a 20% lower adjusted hazard of developing ADRD compared to angiotensin-converting enzyme inhibitor (ACEI) users and a 29% and 18% reduced hazard when compared to non-ARB/ACEI AHM users and AHM non-users (all P < 0.0001). Consumption of BBB-crossing ARBs was linked to a lower hazard of ADRD development than non-BBB-crossing ARBs, undetermined ARBs, and non-consumption of AHMs by 11%, 25%, and 31% (all P < 0.0001). Interpretation: This study suggests that ARBs are superior to ACEIs, non-ARB/ACEI AHMs, or non-use of AHMs in reducing the hazard of ADRD among patients with hypertension. Also, BBB-permeability in ARBs was associated with lower ADRD incidence. There is no cure for AD, ADRD, or vascular dementia; hence, these findings are significant in preventing those disorders in an inexpensive, convenient, and safe way. Limitations in claims data should be considered when interpreting our findings. Funding: This research was supported by the National Institute on Aging grants (R01AG084236, R01AG083039, RF1AG072799, R56AG074604)
Defective differentiation of adipose precursor cells from lipodystrophic mice lacking perilipin 1.
No full textPerilipin 1 (Plin1) localizes at the surface of lipid droplets to regulate triglyceride storage and hydrolysis in adipocytes. Plin1 defect leads to low adiposity in mice and partial lipodystrophy in human. This study investigated the roles of Plin1 in adipocyte differentiation. Plin1 null (-/-) mice showed plenty of multilocular adipocytes and small unilocular adipocytes in adipose tissue, along with lack of a subpopulation of adipose progenitor cells capable of in vivo adipogenesis and along with downregulation of adipogenic pathway. Before initiation of differentiation, adipose stromal-vascular cells (SVCs) from Plin1-/- mice already accumulated numerous tiny lipid droplets, which increased in number and size during the first 12-h induction but thereafter became disappeared at day 1 of differentiation. The adipogenic signaling was dysregulated despite protein level of PPARγ was near normal in Plin1-/- SVCs like in Plin1-/- adipose tissue. Heterozygous Plin1+/- SVCs were able to develop lipid droplets, with both the number and size more than in Plin1-/- SVCs but less than in Plin1+/+ SVCs, indicating that Plin1 haploinsufficiency accounts for attenuated adipogenesis. Aberrant lipid droplet growth and differentiation of Plin1-/- SVCs were rescued by adenoviral Plin1 expression and were ameliorated by enhanced or prolonged adipogenic stimulation. Our finding suggests that Plin1 plays an important role in adipocyte differentiation and provides an insight into the pathology of partial lipodystrophy in patients with Plin1 mutation
